What you carry at this position in your DNA and what research says about it.
Melanoma and Cancer Risk: 7/10 evidence, 6 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): A/A
Typical Cancer Risk
You do not carry the high-risk C variant in the CDKN2A gene. Your genetic risk for hereditary melanoma, pancreatic cancer, and neural system tumors is typical.
What this genotype means: Typical risk of melanoma; Typical risk of pancreatic cancer.
Sample genotype (not yours): A/C
High Melanoma and Cancer Risk
Carrying one copy of the C variant significantly increases your risk of developing cutaneous melanoma, pancreatic cancer, and neural system tumors.
What this genotype means: Significantly increased risk of melanoma; Increased risk of pancreatic cancer; Increased risk of neural system tumors.
Sample genotype (not yours): C/C
Carrying two copies of the C variant is extremely rare and significantly increases your risk of developing cutaneous melanoma, pancreatic cancer, and neural system tumors.
Gene function and biological role
Gene Function: The CDKN2A gene encodes two distinct tumor suppressor proteins, p16INK4a and p14ARF, which play crucial roles in regulating the cell cycle. The p16 protein acts as an inhibitor of cyclin-dependent kinases CDK4 and CDK6, preventing abnormal cell division. Mutations in this gene can compromise its ability to suppress tumor growth, leading to uncontrolled cellular proliferation. CDKN2A is one of the most well-established susceptibility genes for hereditary cutaneous melanoma [1]. Families carrying pathogenic variants in this gene often exhibit a dual predisposition to melanoma and pancreatic cancer [2].
Variant Impact: The rs104894099 variant represents a missense mutation in the second exon of the CDKN2A gene, resulting in an amino acid substitution. This change is commonly designated as p.Ser73Arg or p.Val59Gly depending on the specific protein transcript analyzed. Functional studies indicate that this alteration impairs the p16 protein's ability to bind with CDK4 and CDK6, reducing its capacity to arrest cell division [3]. The variant has been identified in multiple melanoma-prone families, particularly of Mediterranean and Spanish ancestry [4] [5]. It is classified as a pathogenic risk factor that is inherited in an autosomal dominant manner.
Key Insight: This variant is inherited in a dominant pattern, meaning only one copy of the risk allele is needed to significantly increase cancer susceptibility.
Location: CDKN2A. Chromosome 9 · 9p21.3 · 22.0 Mb
Estimated prevalence by population
No frequency data available
This variant is not present in the gnomAD database.
Showing effects for A/A genotype
Cancer & Oncology
Skin Cancer
Melanoma. Evidence: 7/10. Source: PMID 9425228. Typical Risk.
Atypical Mole Syndrome. Evidence: 7/10. Source: PMID 21893440. Typical Risk.
Gastrointestinal Cancers
Pancreatic Cancer. Evidence: 7/10. Source: PMID 29543703. Typical Risk.
Brain & Nervous System Cancers
Brain Tumor. Evidence: 7/10. Source: PMID 20653773. Typical Risk.
Showing effects for A/C genotype
Melanoma. Evidence: 7/10. Source: PMID 9425228. High Risk.
Atypical Mole Syndrome. Evidence: 7/10. Source: PMID 21893440. High Risk.
Pancreatic Cancer. Evidence: 7/10. Source: PMID 29543703. High Risk.
Brain Tumor. Evidence: 7/10. Source: PMID 20653773. High Risk.
Showing effects for C/C genotype
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
This genotype represents the typical, non-risk genetic profile at this locus. You do not carry the pathogenic C allele associated with hereditary cancer syndromes. Your risk of developing cutaneous melanoma, pancreatic cancer, or neural system tumors from this specific gene is not elevated. Studies of melanoma-prone families show that those without CDKN2A mutations have a much lower incidence of these cancers [1]. While general sun safety and routine skin checks remain important for everyone, you do not have the high-risk genetic predisposition linked to this variant [2]. Breast cancer risk is also not elevated by this variant [3]. Overall, your genetic risk at this marker is typical.
Typical risk of melanoma; Typical risk of pancreatic cancer.
Sample genotype: AC (Heterozygous)
Carrying one copy of the C allele significantly increases your lifetime risk of developing cutaneous malignant melanoma [1]. This variant is inherited in an autosomal dominant pattern, meaning a single copy is sufficient to elevate cancer susceptibility. It is also strongly associated with melanoma-pancreatic cancer syndrome, which increases the risk of pancreatic malignancies [2]. Families with this mutation may also present with neural system tumors, such as astrocytomas, or atypical mole syndrome [3]. Regular dermatological screenings and professional skin examinations are highly recommended to detect any changes early. Discussing these findings with a genetic counselor or physician can help establish a personalized cancer surveillance plan, which may include pancreatic imaging. Avoiding excessive sun exposure and using high-SPF sunscreen are critical preventive measures.
Significantly increased risk of melanoma; Increased risk of pancreatic cancer; Increased risk of neural system tumors.
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele is extremely rare and is associated with a very high risk of developing cutaneous melanoma and pancreatic cancer [1]. This genotype represents a homozygous state for a dominant pathogenic variant, which is rarely observed in the general population. The severe impairment of the p16 tumor suppressor protein significantly compromises cell cycle regulation, leading to a high susceptibility to multiple primary melanomas [2]. There is also a strong predisposition to pancreatic cancer and neural system tumors [3].
Variants with shared genetic architecture
rs3731211 · CDKN2A Gene · Chr 9 · Breast Cancer Risk
rs104894094 · CDKN2A Gene · Chr 9 · Hereditary Cancer Risk
rs104894097 · CDKN2A Gene · Chr 9 · Melanoma and Cancer Risk
Novel CDKN2A mutation detected in Spanish melanoma pedigree.
Germline mutations in CDKN2A are infrequent in female patients with melanoma and breast cancer.
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