p53 codon 72 polymorphism producing two functionally distinct proteins — Arg72 with stronger apoptotic activity, Pro72 favoring cell cycle arrest and DNA repair — with population data associating Pro/Pro with ~3 years longer median lifespan

3'UTR variant in the appetite-suppression gene POMC that disrupts miRNA binding sites, altering mRNA stability and melanocortin satiety signaling

Near-gene regulatory variant tagging an IRF5 haplotype that elevates interferon production and increases risk for lupus, systemic sclerosis, Sjögren syndrome, and seropositive rheumatoid arthritis

Pathogenic missense variant in sepiapterin reductase that abolishes BH4 biosynthesis, causing dopamine and serotonin deficiency in the brain; homozygosity or compound heterozygosity causes DOPA-responsive dystonia (SPR deficiency, OMIM

Pathogenic missense variant in CYP17A1 causing complete loss of 17α-hydroxylase/17,20-lyase activity; homozygotes develop 17α-hydroxylase deficiency (hypertension, hypokalemia, and sexual infantilism), while heterozygous carriers show subclinical enzyme reduction detectable by ACTH stimulation testing.

Pathogenic missense variant in the cardiac regulatory myosin light chain causing early-onset severe hypertrophic cardiomyopathy with high risk of sudden cardiac death

Rare NOD2 missense variant (Ser431Leu) that reduces NF-κB activation in response to bacterial muramyl dipeptide, independently associated with Crohn's disease risk; often co-inherited on a haplotype with the V793M variant

Second strongest genetic risk factor for age-related macular degeneration, affecting complement activation and retinal cell oxidative stress

3'UTR variant in the NADPH oxidase p22-phox subunit affecting superoxide generation and vascular oxidative stress

Synonymous exon 4 variant in the cannabinoid receptor 1 gene; near an exon splice enhancer, it alters CB1 mRNA stability and modulates vulnerability to cannabis-induced brain changes, PTSD after trauma, and antidepressant treatment response