The causal ACE insertion/deletion structural variant — presence or absence of a 287-bp Alu element in intron 16 drives ACE enzyme levels, with the I allele lowering ACE activity (endurance advantage) and the D allele raising it (power/strength adaptation)

Regulatory variant in the CCR5 promoter that reduces CCR5 expression by ~45%; the G allele lowers surface CCR5 density on immune cells, slowing HIV disease progression, while the A allele drives higher CCR5 levels and greater monocyte recruitment to atherosclerotic plaques

Missense IRS2 variant where Asp/Asp homozygotes are twice as likely to reach extreme old age — mediates longevity via reduced insulin/IGF-1 signaling, but its protective effect reverses sharply with obesity

Likely-pathogenic GCK missense variant (p.Phe316Tyr) causing glucokinase loss of function; heterozygous carriers have a raised glucose set point producing lifelong mild fasting hyperglycemia consistent with maturity-onset diabetes of the young type 2 (MODY2/GCK-MODY)

Pathogenic missense variant in cardiac alpha-actin that causes hypertrophic cardiomyopathy, left ventricular noncompaction, and septal defects through impaired sarcomeric force generation.

Cis-regulatory enhancer variant at 15q25.1 that drives CHRNA3 and CHRNA5 expression via chromatin looping, independently associated with nicotine dependence and lung cancer risk — particularly informative in non-European populations

Missense variant in kinesin family member 6; the Arg allele was associated with elevated coronary heart disease risk and with substantially greater benefit from statin therapy in the CARE, WOSCOPS, PROSPER, and PROVE IT-TIMI 22 trials, though a large meta-analysis of 19 case-control studies found no independent CAD risk association

The most important Crohn's disease risk variant worldwide — a frameshift insertion in NOD2 that abolishes bacterial muramyl dipeptide sensing; homozygotes face 20–40x elevated Crohn's risk

MAPK signaling variant in MAP2K5 associated with BMI through altered adipogenesis via the MEK5-ERK5 pathway

Intronic variant in RTEL1 (Regulator of Telomere Elongation Helicase 1) on chromosome 20q13.33; the T allele is associated with increased glioma risk and reduced telomere maintenance capacity, linking impaired telomere biology to genomic instability and inflammatory aging