Intronic variant in the mitochondrial folate enzyme MTHFD1L, associated with increased coronary artery disease risk and post-ACS cardiovascular mortality through impaired one-carbon unit supply

Promoter polymorphism that controls PON1 gene expression — the T allele (A on the plus strand) reduces transcription factor binding, halving arylesterase activity and lowering HDL-mediated antioxidant protection against LDL oxidation.

Missense variant in the IL-23 receptor that substitutes leucine for proline at position 310; the rare leucine allele (T) is associated with susceptibility to Graves' disease and rheumatoid arthritis through altered IL-23/Th17 immune signaling

Second most common pathogenic PMM2 allele (p.Phe119Leu); in compound heterozygosity with R141H produces the classic PMM2-CDG phenotype with cerebellar hypoplasia, intellectual disability, and multi-organ glycosylation failure; homozygosity is likely lethal

3' UTR variant in CCDC170 at the 6q25.1 estrogen-signaling locus; the T allele disrupts a miR-27a binding site, reducing CCDC170 expression and increasing breast cancer risk (OR 1.38 in Chinese women); the same locus independently confers endometriosis susceptibility

Synonymous MTRR variant (c.1911G>A) associated with congenital heart disease risk in offspring and maternal carriers, likely through regulatory effects on B12 recycling capacity

Missense variant in the extracellular domain of the IL-4 receptor alpha chain that increases IL-4 signaling sensitivity; the Val75 (G) allele is found in 80% of allergic bronchopulmonary aspergillosis patients and elevates IgE-driven Th2 immune responses in asthma and atopic disease

Recessive pathogenic APP missense variant causing early-onset Alzheimer's disease in homozygotes; heterozygous carriers are unaffected due to a dominant-negative inhibition of amyloid aggregation

Synonymous exon 13 variant in the insulin receptor gene; the A allele has been associated with schizoaffective disorder and modestly with body height in psychiatric cohort studies

Intronic variant in CYP2J2 that tags reduced epoxyeicosatrienoic acid (EET) production, lowering the vasodilatory and cardioprotective signaling molecules derived from arachidonic acid