What you carry at this position in your DNA and what research says about it.
Folate and Choline Metabolism: 5/10 evidence, 27 publications.
You're viewing every possible genotype for this variant.
None of these is your result. Use the genotype toggle to compare them, then sign up and upload your DNA to see which one is yours.
Sample genotype (not yours): G/G
Typical Folate Processing and Lower Birth Defect Risk
Normal MTHFD1 enzyme stability supports typical folate metabolism and baseline birth defect risks. Dietary choline requirements remain at standard levels.
What this genotype means: Typical folate enzyme stability; Baseline risk of neural tube defects; Standard dietary choline requirements.
Sample genotype (not yours): A/A
Reduced Enzyme Stability and Higher Choline Requirements
Two variant alleles significantly reduce MTHFD1 enzyme stability. This is linked to a higher risk of folate-sensitive birth defects and a significantly increased need for dietary choline.
What this genotype means: Significantly reduced folate enzyme stability; Increased risk of neural tube and heart defects; High dietary choline requirement.
Sample genotype (not yours): G/A
Slightly Reduced Enzyme Stability and Increased Choline Demand
A single variant allele slightly reduces the stability of the MTHFD1 enzyme. This can modestly increase the risk of folate-sensitive birth defects and raise the dietary requirement for choline.
What this genotype means: Reduced folate enzyme stability; Modestly increased risk of birth defects; Elevated dietary choline requirement.
Gene function and biological role
Gene Function: The MTHFD1 gene encodes a crucial trifunctional enzyme that regulates folate-mediated one-carbon metabolism [1]. This metabolic network is essential for synthesizing nucleotides and supporting methylation reactions throughout the body [2]. Proper functioning of this enzyme is particularly critical during early embryonic development when rapid cell division occurs [3]. When the folate pathway is less efficient, the body's demand for alternative methyl donors like choline increases [4].
Variant Impact: The rs2236225 variant represents a missense mutation (p.Arg653Gln) in the MTHFD1 gene that alters a single amino acid from arginine to glutamine [3]. This specific change does not completely destroy enzyme activity, but it significantly reduces the enzyme's stability and half-life [3]. As a result, individuals carrying the variant allele have a less stable enzyme, which can impair folate processing and elevate homocysteine levels [5]. This instability also increases the dietary requirement for choline to compensate for the less efficient folate pathway [4].
Key Insight: The MTHFD1 enzyme is so vital that complete loss of its function is not compatible with life, but common variants like rs2236225 simply reduce its stability. When folate levels are low, carriers of this variant rely heavily on dietary choline from foods like eggs to maintain essential cellular methylation.
Location: MTHFD1. Chromosome 14 · 14q23.3 · 64.4 Mb
Estimated prevalence by population
Global 39.0%; European 30.0%; African 62.2%; East Asian 60.6%; South Asian 24.5%; Americas 23.1%; Ashkenazi 31.8%; Finnish 30.7%; Middle Eastern 32.3%; Amish 16.7%.
Estimated GG genotype frequency.
Global 44.6%; European 49.5%; African 33.4%; East Asian 34.5%; South Asian 50.0%; Americas 49.9%; Ashkenazi 49.2%; Finnish 49.4%; Middle Eastern 49.1%; Amish 48.3%.
Estimated GA genotype frequency.
Global 16.4%; European 20.5%; African 4.5%; East Asian 4.9%; South Asian 25.5%; Americas 27.0%; Ashkenazi 19.0%; Finnish 19.9%; Middle Eastern 18.7%; Amish 35.0%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Rare Genetic Disorders
Congenital Malformations
Neural Tube Defects. Evidence: 4/10. Source: PMID 16552426. Typical Risk.
Congenital Heart Defect. Evidence: 3/10. Source: PMID 18767138. Typical Risk.
Nutrition & Metabolism
Vitamin & Mineral Metabolism
Choline Dependency. Evidence: 3/10. Source: PMID 25921832. Typical Demand.
Pharmacogenomics
Immunosuppressant & Biologic Response
Methotrexate Toxicity. Evidence: 5/10. Source: PMID 22074251. Typical Toxicity.
Endocrine & Reproductive
Pregnancy & Birth Complications
Gestational Diabetes. Evidence: 5/10. Source: PMID 38435941. Typical Risk.
Showing effects for A/A genotype
Neural Tube Defects. Evidence: 4/10. Source: PMID 16552426. ~1.5x Increased Risk.
Congenital Heart Defect. Evidence: 3/10. Source: PMID 18767138. Increased Risk.
Choline Dependency. Evidence: 3/10. Source: PMID 25921832. High Demand.
Methotrexate Toxicity. Evidence: 5/10. Source: PMID 22074251. Higher GI Toxicity.
Gestational Diabetes. Evidence: 5/10. Source: PMID 38435941. Lower Risk.
Showing effects for G/A genotype
Neural Tube Defects. Evidence: 4/10. Source: PMID 16552426. Increased Risk.
Choline Dependency. Evidence: 3/10. Source: PMID 25921832. Increased Demand.
Methotrexate Toxicity. Evidence: 5/10. Source: PMID 22074251. Altered Sensitivity.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Two copies of the common G allele allow the MTHFD1 enzyme to maintain its typical stability and half-life [1]. This normal enzyme function supports efficient folate-mediated one-carbon metabolism, which is crucial for DNA synthesis and cellular methylation [1]. Consequently, mothers with this genotype have a baseline risk for having children with neural tube defects [2] or congenital heart defects [1]. Furthermore, there is no genetically driven increase in the requirement for dietary choline, allowing the body to process homocysteine normally [3]. In medical settings, this genotype is associated with standard responses and typical toxicity profiles when undergoing methotrexate therapy [4].
Typical folate enzyme stability; Baseline risk of neural tube defects; Standard dietary choline requirements.
Sample genotype: AA (Homozygous)
Two copies of the variant A allele compromise the stability and half-life of the MTHFD1 enzyme [1]. This genetic status can lead to a less efficient folate pathway, which increases the body's dependence on dietary choline to maintain proper methylation [2]. Maternal carriers with this genotype have an estimated 1.5-fold to 1.7-fold higher risk of having children with neural tube defects [3] or congenital heart defects [1]. Ensuring adequate intake of folate and choline before and during pregnancy is particularly important to support healthy development [4]. In clinical scenarios, this genotype is also associated with an increased risk of specific toxicities, such as gastrointestinal side effects, during methotrexate therapy [5].
Significantly reduced folate enzyme stability; Increased risk of neural tube and heart defects; High dietary choline requirement.
Sample genotype: GA (Heterozygous)
A single copy of the variant A allele leads to a less stable MTHFD1 enzyme, which has a shorter half-life in cells [1]. This reduction in stability can subtly impair the folate pathway, making adequate dietary intake of folate and choline highly important [2]. Maternal carriers of this genotype may experience a modest increase in the risk of having children with neural tube defects [3] or congenital heart defects [1]. To compensate for the less efficient folate cycle, the body often relies more heavily on alternative pathways that consume dietary choline [4]. Additionally, this genotype has been linked to altered sensitivity and potential side effects during methotrexate treatment [5].
Reduced folate enzyme stability; Modestly increased risk of birth defects; Elevated dietary choline requirement.
Variants with shared genetic architecture
rs1950902 · MTHFD1 Gene · Chr 14 · Folate Metabolism
rs3733890 · BHMT Gene · Chr 5 · Homocysteine and Methylation
rs1801133 · MTHFR Gene · Chr 1 · Folate Processing
Maternal and infant gene-folate interactions and the risk of neural tube defects.
Content updated August 2026.
ReadYourDNA provides educational interpretation of DNA data you already have. It is not diagnostic, not a substitute for professional medical advice, diagnosis, or treatment, and is not intended to diagnose, treat, cure, or prevent any disease. Talk to a clinician before acting on any result.
Raw DNA Data Reports for 23andMe & AncestryDNA · About ReadYourDNA · FAQ · Methodology & Science · Pricing · Support and complaints · Legal & Contact · Health Traits · Pharmacogenomics · Carrier Status · Variant Explorer · The Human Karyotype · Privacy Policy · Terms of Service · Accessibility · Consumer Health Data Privacy · Your Privacy Choices · Editorial Standards · Your Data, Checkable · Sample Report · ReadYourDNA and Promethease compared · What is inside a 23andMe raw data file · What is inside an AncestryDNA raw data file · What a chatbot can and cannot do with your raw DNA file · Where a raw DNA file can still be uploaded in 2026
Written, maintained and operated by Martin Pechhacker, sole proprietor, Vienna, Austria. Trade register GISA 40064420. support@readyourdna.com