Intronic variant near TNFAIP3 that tags a 6q23 haplotype strongly associated with SLE and Sjogren's syndrome through impaired A20 ubiquitin-editing activity and NF-kB dysregulation

Pathogenic missense variant in von Willebrand factor causing intracellular retention of the mutant protein; homozygosity causes severe type 3 von Willebrand disease, heterozygous carriers typically have reduced VWF levels and mild bleeding symptoms

Missense variant in PCSK1 that causes a Gln665Glu substitution in the C-terminal domain of prohormone convertase 1/3 (PC1/3), reducing enzyme activity and impairing cleavage of proinsulin to insulin, POMC to alpha-MSH, and proglucagon to GLP-1; the first of a near-obligate coding haplotype (Q665E/S690T, rs6234/rs6235) associated with modest but well-replicated obesity risk across European populations

Rare intronic variant in EIF2AK3-AS1, an antisense long non-coding RNA that regulates expression of EIF2AK3 (PERK), the kinase mediating the endoplasmic reticulum unfolded protein response; PERK pathway activation is documented in endometriotic tissue, linking ER stress to ectopic lesion survival and ovarian damage in endometriosis

Regulatory variant upstream of NFKBIA that specifically elevates risk of psoriatic arthritis over skin-only psoriasis, with a 3.2-fold odds ratio distinguishing arthritic from cutaneous-only disease in psoriasis patients

Intronic variant in the autophagy regulator CLEC16A that alters thymic T-cell selection and immune tolerance, influencing risk for type 1 diabetes and multiple sclerosis

Regulatory upstream variant in the SLC2A9 promoter region; the T allele is associated with modestly elevated serum uric acid in some populations, while the C allele may confer partial protection; independent of the major coding variants at this locus and likely acts through altered GLUT9 transcriptional regulation

Pathogenic nonsense variant introducing a premature stop codon at position 171 of 3β-hydroxysteroid dehydrogenase type II, abolishing conversion of Δ5-steroids to Δ4-steroids in adrenal glands and gonads; homozygotes develop severe salt-wasting congenital adrenal hyperplasia with deficiency of cortisol, aldosterone, and sex steroids.

Intronic/3'UTR GCH1 variant tagging reduced tetrahydrobiopterin (BH4) synthesis capacity; the A allele associates with endothelial dysfunction, oxidative stress, and impaired nitric oxide production, with sex-specific effects on blood pressure

Frameshift deletion in C2 exon 6 causing complete complement C2 deficiency, increasing risk of encapsulated bacterial infections and SLE; most common inherited complement deficiency in Europeans