Pathogenic missense in antithrombin III; the A allele causes type II heparin-binding-site (HBS) antithrombin deficiency with heterozygotes carrying 3-5x VTE risk and homozygotes facing severe, often childhood-onset thrombophilia

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

Regulatory variant in IRF4 enhancer affecting melanocyte pigmentation, sun sensitivity, freckling, and melanoma susceptibility

Intronic LIPC variant in intron 1 associated with low HDL risk, predominantly in women; the C allele is the risk allele for reduced HDL-cholesterol levels

An intronic variant in HELQ (helicase, POLQ-like) on chromosome 4q21.23; the A allele is associated with delayed age at natural menopause (+0.238 years/allele, p=6×10⁻¹⁷²), reflecting HELQ's role in maintaining the oocyte DNA-repair capacity that preserves ovarian reserve across the reproductive lifespan

Influences vitamin D synthesis by regulating how much 7-dehydrocholesterol is available for conversion to vitamin D3 in the skin

The most severe gain-of-function PCSK9 mutation, increasing LDLR-binding affinity 10-25-fold to cause extreme LDL elevation and early-onset coronary artery disease in carriers of this rare pathogenic variant

Intronic variant in ZFPM1 (FOG1), the master transcriptional co-regulator of megakaryopoiesis; the A allele is the strongest common GWAS signal for elevated platelet count (p=1×10⁻⁵⁰) and plateletcrit, with implications for thrombotic tendency and cardiovascular risk

Intronic variant in amelogenin X-linked gene affecting enamel mineralization and susceptibility to dental caries and developmental enamel defects

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