Most common European allele for glutaric acidemia type 1; complete loss of GCDH enzyme activity when inherited with a second pathogenic allele, causing striatal necrosis during febrile crises if untreated

Nonsense mutation in the TSHR gene (Trp546Ter) that eliminates functional TSH receptor expression; homozygotes develop severe congenital hypothyroidism; heterozygous carriers may have subclinical TSH elevation warranting monitoring

Frameshift deletion in APOB that truncates apolipoprotein B, causing familial hypobetalipoproteinemia — very low LDL cholesterol with cardiovascular protection but hepatic steatosis risk

Functional FOXO3 intronic variant with allele-specific CTCF binding and IGF-1-reversible enhancer activity; T allele raises longevity odds ~22% across European cohorts

Intronic variant in PPARGC1A that may modulate PGC-1alpha expression and mitochondrial biogenesis capacity, with a documented interaction with BMI in type 2 diabetes risk

Reduces beta-carotene to retinol (vitamin A) conversion efficiency, contributing to the "poor converter" phenotype

Intronic PTPN22 variant in a transcription factor-binding site, associated with type 1 diabetes in Asian populations where the R620W coding variant is absent

Regulatory variant near the NPR3 natriuretic peptide clearance receptor gene associated with gestational hypertension and preeclampsia risk; the C allele may increase NPR3-mediated peptide clearance, impairing vasodilatory natriuretic signaling during pregnancy

Intronic variant in the TRAF3IP2 locus that lies within the antisense lncRNA TRAF3IP2-AS1 and amplifies IL-17 pathway dysregulation; the G allele is a gain-of-function mutation enhancing SRSF10 recruitment that suppresses IRF1-driven Act1 transcription; the G allele independently associates with psoriasis (OR=1.69) and co-occurs on a secondary risk haplotype (OR=1.8) alongside the primary risk haplotype carrying rs13210247_A (OR=2.7)

9p21 locus variant in the ANRIL long non-coding RNA gene associated with intracranial aneurysm and coronary artery disease, with the T allele increasing arterial disease risk across multiple vascular beds