The most common and clinically severe MEFV mutation, converting methionine to valine at codon 694 of pyrin; homozygous carriers typically develop full familial Mediterranean fever with early onset, frequent attacks, and high amyloidosis risk if untreated with colchicine

Missense variant encoding the Ser690Thr substitution in the C-terminal domain of prohormone convertase 1/3 (PC1/3); paired with rs6234 (Q665E) in near-complete LD to form the Q665E-S690T haplotype that reduces PC1/3 enzymatic efficiency, impairing proinsulin-to-insulin conversion and POMC processing to satiety peptides, and conferring modest obesity risk

An intronic variant in SYNE1 (Nesprin-1) at the 6q25.1 locus, first identified as a genome-wide significant endometriosis locus in the 2017 Sapkota meta-analysis and confirmed in the 2023 Rahmioglu mega-GWAS; the G allele is associated with endometriosis risk overall (OR ~1.11) and strongly enriched for pain subphenotypes including dysmenorrhea (OR ~1.49) and dyspareunia (OR ~2.07), implicating a neuromechanical rather than purely hormonal pathway

Intronic RABEP1 variant associated with rheumatoid arthritis risk, acting through endosomal trafficking and autophagy pathways that regulate antigen processing in immune cells

Intronic variant in the interferon lambda receptor 1 gene that elevates PsA risk by amplifying IL-29/IFN-lambda signaling in synovial tissue, marking those with skin psoriasis who are at elevated risk for progressing to joint disease

Intronic regulatory variant physically located in PDILT that controls uromodulin (Tamm-Horsfall protein / UMOD) expression — the strongest genetic predictor of longitudinal kidney function decline in the general population. Catalog gene attribution is UMOD (the regulatory target and clinically relevant gene); physical location is PDILT (adjacent gene in the same LD block).

Intronic variant within the SHBG gene that participates in a haplotype (with rs727428) lowering circulating sex hormone-binding globulin levels, increasing bioavailable testosterone and estradiol; lower SHBG is linked to PCOS susceptibility, insulin resistance, type 2 diabetes risk, and female VTE risk mediated by estradiol

Missense variant in complement component C2 forming a protective haplotype with CFB that reduces age-related macular degeneration risk by ~45-50%

Intergenic regulatory variant near TBX21 associated with allergic asthma susceptibility; G allele homozygosity carries markedly elevated asthma risk through reduced T-bet-driven Th1 immune tone

Intronic MAPT variant that directly regulates tau exon 3 splicing via differential hnRNP F/Q binding; the G allele (H1 haplotype) reduces exon 3 inclusion, elevating 4-repeat tau isoforms and increasing risk for Parkinson's disease, PSP, and corticobasal degeneration