Missense variant in the C2A calcium-binding domain of presynaptic scaffolding protein Piccolo, altering monoamine vesicle release efficiency and modulating HPA axis reactivity — associated with elevated depression risk and altered antidepressant treatment response

Missense variant in WNT16 that substitutes glycine for arginine at position 82, reducing cortical bone mineral density and increasing fracture risk

Protective loss-of-function variant in the PTPN22 catalytic domain that reduces phosphatase activity and lowers risk of SLE, RA, and ulcerative colitis

Pathogenic missense variant in argininosuccinate lyase that reduces urea cycle enzyme activity, causing argininosuccinic aciduria when inherited in biallelic form; heterozygous carriers are typically asymptomatic but carry the allele at reproductive risk

3' UTR regulatory variant in LPIN2 (lipin 2) that alters fat distribution and insulin sensitivity, with risk for type 2 diabetes that is amplified by obesity

Intronic GWAS variant in the TRAF1-C5 locus on chromosome 9 robustly associated with seropositive rheumatoid arthritis risk

Missense variant in TLR3 that halves dsRNA-binding capacity, reducing antiviral interferon responses and increasing susceptibility to several viral infections

Missense variant in the elastin-crosslinking enzyme LOXL1; the common G allele is one of the strongest known genetic risk factors for exfoliation syndrome and exfoliation glaucoma, a leading cause of secondary glaucoma worldwide

Rare missense variant in the biotinidase enzyme (p.Pro167Ser); a likely pathogenic allele for biotinidase deficiency. Heterozygous carriers have reduced but usually sufficient biotinidase activity; compound heterozygosity with other BTD pathogenic variants can cause partial or profound deficiency requiring lifelong biotin supplementation.

Ultra-rare autosomal recessive MYBPC3 missense variant; homozygotes develop severe HCM while heterozygous carriers remain clinically unaffected up to age 71 in the single reported family