Loss-of-function variant that naturally lowers LDL cholesterol by 15-28% and reduces coronary disease risk by up to 47%

Missense variant that reduces ANGPTL4's inhibition of lipoprotein lipase, lowering fasting triglycerides and decreasing coronary artery disease risk in carriers of the K40 allele

Missense variant in the innate immune kinase ALPK1 (Met861Thr); the C allele is associated with elevated gout risk in East Asian populations through altered URAT1-mediated urate homeostasis and NF-κB inflammatory signaling

ACADVL missense variant (p.Phe458Leu) classified likely pathogenic for VLCAD deficiency; heterozygous carriers are asymptomatic but important to identify for reproductive counseling

Intronic regulatory variant in TSHR intron 1; the T allele disrupts thymic expression of the TSH receptor, allowing autoreactive T cells to escape tolerance and increasing susceptibility to Graves' disease — the most common autoimmune cause of hyperthyroidism

Pathogenic missense variant in the ZIP4 intestinal zinc transporter causing hereditary acrodermatitis enteropathica when homozygous; heterozygotes are asymptomatic carriers

Missense variant in antithrombin (SERPINC1) that impairs heparin-catalyzed thrombin inhibition, causing type II reactive-site antithrombin deficiency and approximately 10-fold increased venous thromboembolism risk

Ashkenazi Jewish founder missense mutation in coagulation factor XI causing impaired FXI dimerization; homozygotes develop hemophilia C (severe FXI deficiency) with post-surgical and trauma-related bleeding, while heterozygotes have partial deficiency with variable bleeding risk; the most prevalent FXI deficiency allele in Ashkenazi Jewish populations

Intronic variant in the ENAM enamelin gene associated with altered dental caries susceptibility across multiple populations, with the reference A allele linked to increased caries risk and the alternate G allele to a protective effect

Missense variant in the linker region of XRCC1 that disrupts interaction with the OGG1 glycosylase, impairing base excision repair of oxidative DNA damage; effect direction varies by cancer type and ancestry