Promoter variant that increases CTLA-4 transcription; T allele carriers show better response to abatacept in rheumatoid arthritis and may have modestly altered autoimmune susceptibility

Pathogenic missense variant in junctophilin-2 that disrupts sarcoplasmic reticulum coupling and calcium signaling, causing hypertrophic cardiomyopathy with high age-dependent penetrance

Rare missense variant in the keratinocyte NF-κB scaffold protein CARD14 that may predict favorable response to anti-TNF biologic therapy in psoriasis patients

Missense variant in von Willebrand factor (p.Asp141Gly) associated with type 1 von Willebrand disease; heterozygous and homozygous carriers may have reduced VWF activity and increased bleeding tendency requiring hematology evaluation

APOL1 G1 kidney disease risk variant — missense change that evolved for trypanosome resistance but causes nephropathy in the recessive state

Missense variant in CPT2 that destabilizes the carnitine palmitoyltransferase 2 enzyme, impairing mitochondrial uptake of long-chain fatty acids and causing recurrent exercise- and fever-induced rhabdomyolysis in homozygotes; the most common cause of adult myopathic CPT II deficiency in Europeans.

Obesity GWAS missense variant in SH2B1 that impairs leptin signaling and increases visceral fat and type 2 diabetes risk

Promoter variant in FCRL3 that alters NF-κB binding and elevates FCRL3 expression on B cells and regulatory T cells, increasing susceptibility to rheumatoid arthritis, Graves' disease, and Hashimoto's thyroiditis

Promoter variant in UGT1A1 that tags the *28 reduced-expression haplotype; T allele carriers have lower hepatic UGT1A1 expression, mildly elevated unconjugated bilirubin (Gilbert syndrome spectrum), and altered metabolism of bilirubin, atazanavir, and irinotecan

Intergenic tag SNP upstream of HLA-DRA; the G allele is the primary GWAS signal for rheumatoid arthritis susceptibility in the HLA class II region, with among the strongest effect sizes of any common RA variant (OR ~2.47 in Europeans).