Pathogenic variants (disease-causing) in the CDKN2A gene (also known as p16) can affect two different proteins in our body – p16INK4a and p14ARF. Pathogenic variants impacting p14ARF are associated with an increased risk of melanoma and brain tumors while variants that impact the p16INK4a protein increase the risk of developing melanoma and pancreatic cancer. Families with pathogenic variants in CDKN2A often show multiple cases of melanoma, sometimes at younger ages than the general population. Management of SDHD–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early. CDKN2A variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in CDKN2A exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
