Triallelic missense variant in the P-glycoprotein efflux pump that reduces the transporter's ability to expel xenobiotics — including environmental toxicants such as pesticides, heavy metals, and endocrine disruptors — from gamete-forming cells, potentially increasing DNA damage susceptibility in oocytes and spermatocytes

Rare loss-of-function missense variant in the cardiac sodium channel Nav1.5 causing congenital sick sinus syndrome through altered channel inactivation kinetics

Upstream regulatory variant of the cold-sensing TRPM8 channel that modulates migraine susceptibility, cold pain sensitivity, and brown adipose thermogenesis

GLP-1 receptor variant in intracellular loop 2 that alters receptor surface expression and signaling, influencing antipsychotic response and cortisol regulation

ENPP1 K121Q variant that increases ENPP1 binding affinity to the insulin receptor by 2–3 fold, blunting insulin signaling and raising insulin resistance risk.

Pathogenic missense variant abolishing 17α-hydroxylase/17,20-lyase activity, causing combined cortisol and sex steroid deficiency with mineralocorticoid excess

Phase I detoxification enzyme that activates polycyclic aromatic hydrocarbons and metabolizes estrogens; the Val variant increases catalytic activity, producing more reactive intermediates

Missense variant in alpha-dystrobrevin disrupting the EF-hand calcium-binding domain, associated with left ventricular noncompaction cardiomyopathy in a single Japanese family

Intronic IL23R variant in LD block 2 where the T allele is associated with increased susceptibility to Crohn's disease and ankylosing spondylitis while the C allele is protective — a signal distinct from the rs1004819/rs7517847 haplotype block

CHRNA3 synonymous variant in the nicotinic receptor gene cluster strongly associated with heavy smoking, nicotine dependence, lung cancer, and COPD, with independent effects in non-European populations