A regulatory variant upstream of PIWIL1 on chromosome 12, in a CpG region of the gene's promoter; the A allele is associated with earlier age at natural menopause via a recessive mechanism, linking piRNA-pathway genome surveillance in oocytes to ovarian reserve and reproductive lifespan

Intronic variant in IGFBP3 — the gene encoding the main carrier protein for IGF-1 in circulation — associated with lower circulating IGFBP-3 levels in carriers of the G allele

The most common pathogenic PMM2 variant, causing phosphomannomutase 2 deficiency and PMM2-CDG (congenital disorder of glycosylation type Ia) when inherited in compound heterozygous form; homozygous R141H is embryonic lethal

Triallelic promoter variant that strongly influences basal CRP transcription; the T (coding) and A (coding) alleles both increase CRP expression, with the A allele having the largest effect on circulating CRP levels

Missense variant in Act1 that abolishes IL-17 signaling by disrupting TRAF6 binding, driving paradoxical hyperactivation of Th17 responses and psoriasis susceptibility

Gain-of-function missense variant in the NLRP3 inflammasome sensor that elevates baseline IL-1beta and IL-18 production, increasing susceptibility to gout, inflammatory bowel disease, and metabolic inflammation

Pathogenic missense variant in the myosin motor domain causing hypertrophic cardiomyopathy with a 47% lifetime atrial fibrillation rate in affected adults; requires family cardiac screening

Intronic variant in WNT4 on chromosome 1p36.12 that introduces a high-affinity estrogen receptor alpha binding site, upregulating WNT4 in endometrial stromal cells; the T allele is associated with increased endometriosis and uterine fibroid risk through enhanced stromal invasibility, while the C allele associates with pelvic organ prolapse risk — an example of antagonistic pleiotropy in reproductive tissue biology

NOS3 promoter variant that reduces eNOS expression and increases hypertension risk by disrupting an ETS transcription factor binding site

Missense variant in the VWF D' domain that abolishes high-affinity Factor VIII binding, causing type 2N (Normandy) von Willebrand disease — a recessively-expressed bleeding disorder mimicking mild hemophilia A