Nonsense variant in the aldolase B gene creating a premature stop codon at position 204; pathogenic for hereditary fructose intolerance (HFI), an autosomal recessive disorder causing toxic fructose-1-phosphate accumulation in liver and kidneys when fructose is ingested

Intronic HMGCR variant that modulates alternative splicing of exon 13, producing a truncated Δ13 isoform that reduces statin-binding capacity and attenuates LDL-cholesterol lowering in response to statin therapy

Pathogenic missense variant in riboflavin transporter RFVT2 (p.Leu123Pro) causing Brown-Vialetto-Van Laere syndrome type 2, a rare autosomal recessive neurodegenerative disorder; high-dose riboflavin supplementation is the primary disease-modifying treatment

Pathogenic missense variant in the beta-myosin heavy chain motor domain causing hypertrophic cardiomyopathy through a dominant-negative mechanism; documented in more than 15 unrelated HCM-affected individuals and absent from population databases

Intronic PLG variant tagging a regional haplotype that reduces plasminogen expression, impairing fibrinolysis, macrophage recruitment, and mucosal wound healing — with documented associations with periodontitis susceptibility and plasminogen level variation

Intronic variant in the brain neurosteroid hydroxylase gene affecting DHEA and pregnenolone catabolism, linked to GABAergic tone and anxiety risk in GWAS

Intronic IL6R variant in linkage disequilibrium with the functional Asp358Ala (rs2228145) coding change; the C allele tags a haplotype associated with elevated CRP, LDL, and ApoB and with reduced protection from coronary heart disease risk

Second intronic enhancer variant in SMAD3 that modulates TGF-beta effector signaling in regulatory T cells, influencing susceptibility to autoimmune and inflammatory conditions including IBD and ankylosing spondylitis

Intronic risk variant within TNFAIP3 intron 2 that independently increases susceptibility to rheumatoid arthritis and SLE through a distinct LD block from the nearby intergenic 6q23 signals, completing the three-signal risk model at the TNFAIP3 locus

Nonsense mutation creating a premature stop codon at position 1853 of von Willebrand factor; homozygotes develop severe type 3 VWD with essentially absent VWF and require factor replacement, while heterozygotes typically have mild type 1 VWD