Missense variant in PRIM1 (DNA primase small subunit) that changes aspartate to alanine at position 5 of the protein; the G allele (Asp5Ala) is associated with later age at natural menopause by approximately 0.35 years per copy, implicating DNA replication priming fidelity in the rate of ovarian follicle depletion

Intronic variant in PIEZO1, the endothelial mechanosensory ion channel that senses blood flow shear stress; the G allele is associated with elevated varicose vein risk in genome-wide studies of over 800,000 individuals

Common intronic variant in CACNA1A — the P/Q-type calcium channel gene mutated in familial hemiplegic migraine — that reaches genome-wide significance for migraine with aura; the G (reference) allele confers typical susceptibility while the A allele is mildly protective

Synonymous variant in P-glycoprotein affecting drug efflux pump expression and hundreds of substrate drugs

Pathogenic glucokinase missense variant that nearly abolishes enzyme activity, causing autosomal dominant maturity-onset diabetes of the young type 2 (MODY2) in heterozygous carriers and permanent neonatal diabetes when homozygous

Rare pathogenic nonsense variant in CYP17A1 causing complete abolition of 17α-hydroxylase/17,20-lyase activity; homozygotes develop the full 17α-hydroxylase deficiency phenotype (hypertension, hypokalemia, absent puberty, low cortisol), while heterozygous carriers are clinically unaffected but carry a CYP17A1 loss-of-function allele relevant to reproductive planning.

Rare pathogenic TTR missense variant causing hereditary transthyretin amyloidosis with predominantly central nervous system and oculoleptomeningeal involvement

Missense variant in the diamine oxidase enzyme that contributes to reduced histamine clearance from dietary sources

Intergenic variant near JAK2 that increases JAK2 expression and JAK-STAT signaling, disrupting intestinal barrier function and increasing IBD susceptibility

Intronic variant in the neurotrophin sorting receptor SORCS3, the top GWAS hit for major depression in the Howard et al. 2019 meta-analysis of 807,553 individuals