Promoter insertion/deletion polymorphism that controls PAI-1 (plasminogen activator inhibitor-1) expression; the 4G allele (G on the plus strand) raises PAI-1 levels, suppresses fibrinolysis, and increases risk of venous thromboembolism, myocardial infarction, preeclampsia, and recurrent pregnancy loss

Common missense variant near the BRCA1 RING finger domain; associated with modestly elevated breast cancer risk (OR ~1.1-1.3) but classified as benign/likely benign — not a pathogenic BRCA1 mutation

Missense variant in the MLH1 ATPase domain (c.655A>G, p.Ile219Val) that substitutes isoleucine for valine at a conserved hydrophobic position; classified benign for Lynch syndrome with intact mismatch repair activity, but the G allele shows modest associations with altered DNA repair kinetics and may influence meiotic recombination efficiency

Intronic regulatory variant in CYP2R1 that reduces hepatic vitamin D 25-hydroxylase expression, lowering the rate of vitamin D activation and increasing susceptibility to vitamin D insufficiency

Ultra-rare KCNH2 missense variant substituting asparagine for lysine at position 595 in the C-linker domain, associated with congenital long QT syndrome type 2 through impaired hERG channel function

Intronic variant in kallikrein-4 that encodes the enamel maturation protease; A allele associated with increased caries susceptibility and molar hypomineralization in permanent dentition

Intronic variant near KCNK5 that reduces TASK2 potassium channel expression and increases migraine susceptibility; the T allele is associated with lower KCNK5 expression and an ~5% elevated odds of migraine per allele in the largest GWAS to date.

Pathogenic glucokinase missense variant that nearly abolishes enzyme activity (Kcat/S0.5 ratio 0.0001 vs wild-type), causing autosomal dominant maturity-onset diabetes of the young type 2 (MODY2) in heterozygous carriers — lifelong mild stable fasting hyperglycemia that does not require pharmacological treatment

Pathogenic CYP17A1 missense variant causing combined 17α-hydroxylase/17,20-lyase deficiency; homozygotes lose all sex steroid and cortisol synthesis, developing hypertension, hypokalemia, and absent puberty; heterozygous carriers are asymptomatic but carry reproductive risk

Pathogenic nonsense variant in dystrophin creating a premature stop codon at position 3182, causing X-linked dilated cardiomyopathy and Duchenne/Becker muscular dystrophy with prominent cardiac involvement