Missense variant in the SCAP cholesterol-sensor gene (Val798Ile); the C allele (coding-strand G) impairs the SCAP–SREBP-2 feedback axis, promoting cholesterol accumulation in vascular cells and elevating sudden cardiac death risk in combination with the SREBF2 Gly595Ala variant

Intronic variant in GLT6D1 reducing GATA-3 transcription factor binding in T cells, increasing aggressive periodontitis risk

Missense variant in the CHEK2 FHA domain that impairs phosphoprotein binding and dimerization, conferring moderate-penetrance susceptibility to breast, colorectal, thyroid, prostate, and kidney cancer

Upstream regulatory variant of the cold-sensing TRPM8 channel that modulates migraine susceptibility, cold pain sensitivity, and brown adipose thermogenesis

GLP-1 receptor variant in intracellular loop 2 that alters receptor surface expression and signaling, influencing antipsychotic response, cortisol regulation, and bone metabolism

Intronic GIPR variant that reduces functional GIP receptor expression via altered splicing, impairing the incretin-mediated insulin response while paradoxically lowering BMI

Intronic variant near QDPR that affects BH4 recycling efficiency, influencing neurotransmitter synthesis and nitric oxide production

Missense variant in CYP17A1 reducing both 17α-hydroxylase and 17,20-lyase activities to 40–45% of normal; causes partial combined 17α-hydroxylase/17,20-lyase deficiency with variable sex steroid deficiency, mineralocorticoid excess, and impaired fertility

Pathogenic alpha-tropomyosin missense variant that increases thin filament calcium sensitivity, causing familial hypertrophic cardiomyopathy; a founder mutation accounting for ~6.5% of HCM cases in Finland

Rare NOD2 missense variant (Asn852Ser) that impairs innate immune sensing of bacterial peptidoglycan and is associated with Crohn's disease risk; markedly enriched in Ashkenazi Jewish populations (~1.6%)