What you carry at this position in your DNA and what research says about it.
Macular Degeneration Risk: 8/10 evidence, 23 publications.
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Sample genotype (not yours): T/T
Typical Risk of Macular Degeneration
Carrying two copies of the common T allele is associated with standard levels of complement factor B and a typical baseline risk for age-related macular degeneration. This genotype does not provide the protective effect against retinal inflammation seen in carriers of the minor A allele.
What this genotype means: Typical baseline levels of complement factor B; Standard population risk for age-related macular degeneration.
Sample genotype (not yours): A/A
Significantly Reduced Risk of Macular Degeneration
Carrying two copies of the protective A allele is associated with the lowest levels of complement factor B and a highly reduced risk of age-related macular degeneration. This rare genotype offers maximum genetic protection against retinal inflammation.
What this genotype means: Lowest circulating levels of complement factor B; Highly reduced risk of age-related macular degeneration; Slightly increased susceptibility to chronic fatigue syndrome.
Sample genotype (not yours): T/A
Reduced Risk of Macular Degeneration
Carrying one copy of the protective A allele is associated with lower levels of complement factor B and a significantly reduced risk of age-related macular degeneration. This genetic variant helps shield the retina from excessive inflammatory damage.
What this genotype means: Lower circulating levels of complement factor B; Approximately 50% lower risk of age-related macular degeneration.
Gene function and biological role
Gene Function: The CFB gene encodes complement factor B, a key component of the alternative complement pathway in the innate immune system. This pathway acts as a rapid-response defense mechanism against pathogens and helps clear cellular debris. Complement factor B is cleaved by factor D to yield the active subunit Bb, which participates in the amplification loop of complement activation. Overactivation of this pathway can lead to chronic inflammation and tissue damage, particularly in the retina. Genetic variations in CFB are heavily studied for their role in inflammatory and degenerative diseases, most notably age-related macular degeneration.
Variant Impact: The rs4151667 variant is a missense mutation in the CFB gene that results in the substitution of the amino acid leucine with histidine at position 9 (p.Leu9His). This structural change occurs in the signal peptide region of the complement factor B protein, which can alter its secretion or stability. The minor A allele (His) is widely recognized in genetic literature as a protective factor against age-related macular degeneration. By reducing the overall activity or levels of complement factor B, this variant helps prevent the chronic, low-grade inflammation that damages retinal cells over time.
Key Insight: Carrying the minor A allele of this variant can cut the risk of developing advanced age-related macular degeneration by approximately half. This protective effect is driven by a natural reduction in complement system activation, which prevents inflammatory damage to the retina.
Location: CFB. Chromosome 6 · 6p21.33 · 31.9 Mb
Estimated prevalence by population
Global 93.4%; European 91.0%; African 97.6%; East Asian 95.6%; South Asian 89.2%; Americas 95.0%; Ashkenazi 95.0%; Finnish 89.2%; Middle Eastern 95.3%; Amish 97.4%.
Estimated TT genotype frequency.
Global 6.5%; European 8.8%; African 2.4%; East Asian 4.3%; South Asian 10.4%; Americas 4.9%; Ashkenazi 4.9%; Finnish 10.4%; Middle Eastern 4.6%; Amish 2.6%.
Estimated TA genotype frequency.
Global 0.1%; European 0.2%; African < 0.1%; East Asian < 0.1%; South Asian 0.3%; Americas 0.1%; Ashkenazi 0.1%; Finnish 0.3%; Middle Eastern 0.1%; Amish < 0.1%.
Estimated AA genotype frequency.
Showing effects for T/T genotype
Organ Systems
Vision & Eye Health
Macular Degeneration. Evidence: 5/10. Source: PMID 16518403. Typical Risk.
Immunity & Inflammation
Inflammatory & Circulating Protein Markers
Complement Factor B. Evidence: 8/10. Source: PMID 29875488. Typical Levels.
Chronic Inflammatory Diseases
Chronic Fatigue. Evidence: 3/10. Source: PMID 26116897. Typical Risk.
Showing effects for A/A genotype
Macular Degeneration. Evidence: 5/10. Source: PMID 16518403. Highly Reduced Risk.
Complement Factor B. Evidence: 8/10. Source: PMID 29875488. Lowest Levels.
Chronic Fatigue. Evidence: 3/10. Source: PMID 26116897. Increased Risk.
Showing effects for T/A genotype
Macular Degeneration. Evidence: 5/10. Source: PMID 16518403. ~50% Lower Risk.
Complement Factor B. Evidence: 8/10. Source: PMID 29875488. Lower Levels.
Chronic Fatigue. Evidence: 3/10. Source: PMID 26116897. Slightly Higher Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
This genotype represents the most common genetic profile globally, with about 96% of the population carrying two copies of the T allele. Individuals with this profile have typical baseline levels of complement factor B in their plasma [1]. Because this genotype lacks the protective histidine variant (A allele), there is no genetically driven reduction in complement system activation [2]. Consequently, the risk of developing age-related macular degeneration remains at the standard population baseline, heavily influenced by age, smoking, and other genetic loci like CFH [3]. Maintaining regular eye exams and avoiding smoking are key strategies to protect vision health, as smoking can interact with complement pathway genetics to accelerate retinal damage [4].
Typical baseline levels of complement factor B; Standard population risk for age-related macular degeneration.
Sample genotype: AA (Homozygous)
Carrying two copies of the rare A allele is highly uncommon, occurring in less than 1% of most populations. This genotype is associated with significantly lower levels of complement factor B, leading to a highly dampened alternative complement pathway [1]. The reduction in complement activity provides robust protection against the inflammatory processes that drive age-related macular degeneration [2]. Individuals with this profile are highly unlikely to experience the severe retinal cell deterioration characteristic of advanced macular degeneration [3]. Despite this strong genetic shield, maintaining a healthy lifestyle and protecting the eyes from UV light remain important for long-term vision [4]. Interestingly, some preliminary research suggests that while this variant protects the eyes, it might alter susceptibility to other immune-related conditions like chronic fatigue syndrome [5].
Lowest circulating levels of complement factor B; Highly reduced risk of age-related macular degeneration; Slightly increased susceptibility to chronic fatigue syndrome.
Sample genotype: TA (Heterozygous)
Carrying one copy of the minor A allele (the histidine variant) provides a strong protective effect against age-related macular degeneration [1]. This protective benefit is thought to stem from lower circulating levels of complement factor B, which reduces overactivation of the alternative complement pathway [2]. With less complement activation, the retina is subjected to less chronic, low-grade inflammation and fewer drusen deposits over a lifetime [3]. Studies show that having this genotype can reduce the risk of developing advanced macular degeneration by up to 50% [4]. However, this protective effect can be partially compromised by environmental factors such as smoking, which independently drives complement activation and retinal damage [5].
Lower circulating levels of complement factor B; Approximately 50% lower risk of age-related macular degeneration.
Variants with shared genetic architecture
rs641153 · CFB Gene · Chr 6 · Macular Degeneration Protection
rs1048709 · CFB Gene · Chr 6 · Eye Inflammation Risk
rs12614 · CFB Gene · Chr 6 · Hepatitis B and Eye Health
Genomic atlas of the human plasma proteome.
Genetic markers and biomarkers for age-related macular degeneration.
Content updated August 2026.
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