Intronic variant in the eumelanin enzyme TYRP1 associated with eye and hair color, UV sensitivity, and modestly elevated melanoma risk in Europeans

Missense variant in IL-1α (Ala114Ser) that acts as a common hypomorphic mutation — the minor Serine allele reduces IL-1α secretion by ~50% through post-translational retention; the Serine allele is associated with periodontitis susceptibility and ankylosing spondylitis in Europeans

Second most common inherited thrombophilia; the A allele raises prothrombin levels by 30%, increasing venous thromboembolism risk 2-5 fold and is highly actionable for women considering oral contraceptives

Promoter variant that reduces hepatic lipase activity, raising HDL-C levels but shifting to larger, less protective HDL particles with a genotype-specific dietary fat response

Promoter-region variant in MTTP that reduces hepatic MTTP transcription; the G allele (common) is associated with lower MTTP expression, impaired VLDL secretion, and increased hepatic triglyceride accumulation

Promoter variant in the MLH1 DNA mismatch repair gene that reduces transcriptional activity and predisposes to promoter hypermethylation, increasing colorectal cancer risk through microsatellite instability

Missense variant in MRE11 (p.Met698Val, T>C on plus strand) at a poorly conserved position outside known nuclease or RAD50-interaction domains; classified benign by multiple ClinVar submitters, but MRE11 is a core component of the MRN complex (MRE11-RAD50-NBS1) that initiates homologous recombination repair of DNA double-strand breaks — including in meiotic cells, where MRN is required for crossover formation and spermatogenic integrity

Upstream regulatory variant in CYP2R1 that reduces hepatic 25-hydroxylase expression, lowering the conversion of vitamin D3 to 25(OH)D and predisposing carriers to vitamin D insufficiency

Intergenic variant at chromosome 4q25 near PITX2 — the strongest GWAS signal for atrial fibrillation susceptibility; the T allele reduces PITX2 expression in the left atrium, impairing suppression of a pacemaker program that normally prevents the left atrium from generating ectopic impulses

Intronic IRF6 variant associated with non-syndromic cleft lip with or without cleft palate susceptibility in multiple populations, particularly East Asian ancestry groups