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

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

Pathogenic missense variant in CYP17A1 causing complete loss of 17α-hydroxylase/17,20-lyase activity; homozygotes develop 17α-hydroxylase deficiency (CAH) with absent sex steroids, primary amenorrhea, and mineralocorticoid excess; heterozygous carriers have subclinical steroid biosynthetic abnormalities and should undergo endocrinology evaluation

Stop-gain mutation eliminating connexin 26 function; the most common GJB2 deafness allele in South Asian populations and the ancestral founder mutation carried into European Romani communities