Intronic ATG16L1 variant in tight LD with the T300A coding variant; the G risk allele tags a haplotype that sensitizes the ATG16L1 protein to caspase-3-mediated degradation, impairing autophagy and Paneth cell antimicrobial function, raising risk for Crohn's disease

Missense variant in sorting nexin 19 that alters endolysosomal positioning at the ER membrane; the A allele was associated with elevated coronary heart disease risk in a prospective cohort study and confirmed as one of five common risk variants in the ARIC validation

Intronic variant in the presynaptic scaffold gene PCLO linked to altered monoaminergic neurotransmission, increased depression and anxiety risk, and heightened amygdala reactivity to emotional stimuli

Promoter variant in PTPN22 that alters gene expression and modulates autoimmune susceptibility, particularly in Asian populations where it acts independently of the R620W coding variant

Exon 10 missense variant in the inflammasome regulator pyrin, converting methionine to isoleucine at codon 694; one of five founder FMF mutations, associated with mild-to-moderate familial Mediterranean fever, colchicine responsiveness, and lower amyloidosis risk than M694V — particularly prevalent in East Asian FMF patients and Lebanese founder lineages

Pathogenic missense variant in the hepatic copper transporter ATP7B that abolishes protein trafficking to the trans-Golgi network; the most common Wilson disease mutation in East Asian populations, accounting for ~29% of pathogenic ATP7B alleles in Chinese patients; homozygotes and compound heterozygotes develop progressive copper accumulation causing liver disease, neurological symptoms, and Kayser-Fleischer rings; heterozygous carriers are asymptomatic but can transmit the disease if their reproductive partner also carries an ATP7B pathogenic variant

Upstream regulatory variant near the ghrelin receptor gene; the A allele is associated with abdominal adiposity and metabolic syndrome risk in women through altered GHSR expression

Intronic IL12B variant in linkage with the promoter-regulatory haplotype; T allele is protective against psoriasis and associated with better ustekinumab (anti-p40) response

Common perforin variant that reduces cytolytic activity by ~50%, acting as a susceptibility factor for HLH when combined with a second PRF1 loss-of-function allele

Regulatory variant 2 kb upstream of EIF4EBP1 (encoding 4E-BP1, a direct mTOR effector); the C allele is associated with later age at menopause (beta +0.376 years per allele) and higher circulating AMH, consistent with slower primordial follicle activation through attenuated mTOR signalling