Pathogenic missense variant in the ZIP4 intestinal zinc transporter; homozygosity causes acrodermatitis enteropathica, a rare but fully treatable zinc malabsorption disorder

Intronic PTPN22 variant independently associated with psoriasis and ankylosing spondylitis, operating through a distinct mechanism from the established R620W risk allele

Likely pathogenic missense variant in antithrombin III; the G allele converts Ser148 to Pro, causing type II pleiotropic antithrombin deficiency that reduces both anticoagulant activity and antigen levels, substantially elevating lifetime VTE risk in heterozygous carriers

Nonsense variant in sepiapterin reductase that abolishes BH4 biosynthesis, causing dopamine and serotonin deficiency in the brain; homozygosity leads to DOPA-responsive dystonia (SPR deficiency, OMIM

Tag SNP for HLA-C*06:02, the strongest genetic risk factor for psoriasis, determining disease phenotype and predicting differential response to biologic therapy

Intergenic enhancer variant controlling BNC2 expression in melanocytes; determines pigmentation saturation and freckling tendency with implications for UV sensitivity and skin cancer risk

Coding GCKR variant (Pro446Leu) that directly reduces GCKRP sensitivity to fructose-6-phosphate, constitutively activating hepatic glucokinase and producing the characteristic trade-off of lower fasting glucose and insulin resistance against higher triglycerides, CRP, and NAFLD risk

Intergenic variant 19 kb downstream of lipoprotein lipase (LPL) that tags a regulatory region affecting LPL expression; the rare G allele is associated with meaningfully lower triglycerides and higher HDL cholesterol.

Intronic regulatory variant in SERPINE2 that modulates expression of Protease Nexin-1, the most potent tissue thrombin inhibitor, shifting fibrinolytic balance and elevating venous thromboembolism risk

LDLR missense variant at position 827 within the cytoplasmic NPXY internalization motif; classified as uncertain significance for familial hypercholesterolemia, with conflicting functional and population evidence — the more common G>A change (Val827Ile) shows no LDL uptake impairment in functional assays, while the rarer G>T change (Val827Phe) has been reported in FH patients