Is TAP2 p.Val600= (c.1800A>C) pathogenic?

TAP2 p.Val600= (c.1800A>C) is classified Benign in TAP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with MHC class I deficiency.

What condition is associated with TAP2 p.Val600= (c.1800A>C)?

TAP2 p.Val600= (c.1800A>C) is associated with MHC class I deficiency (ClinVar).

TAP2 p.Val600=

Q: How common is TAP2 p.Val600= (c.1800A>C) in the general population?

TAP2 p.Val600= (c.1800A>C) is common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Immunodeficiency by defective expression of MHC class I inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1800A>C · rs2229527 · VCV403514

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -8.4	GERP -4.1
Overall
CADD	0.176	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.2% African / African-American · 7,613/74,988 alleles

Filtering AF 9.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.88%

Overall 5.08% 81,954/1,613,994 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.2%	10
Finnishnot grpmax-eligible	9.86%	10
Amishnot grpmax-eligible	6.25%	16
European (non-Finnish)	5.02%	20
East Asian	4.54%	22
Remaining individualsnot grpmax-eligible	4.33%	23
Admixed American	3.11%	32
Ashkenazi Jewishnot grpmax-eligible	2.94%	34
Middle Eastern	2.66%	38
South Asian	1.19%	84

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TAP2
Protein: p.Val600=
Coding: c.1800A>C
MANE Select: NM_174975 · reported on NM_001290043
dbSNP: rs2229527
Type: single nucleotide variant
Location: chr6:32829532 (GRCh38)
Structure: AlphaFold pLDDT 96.96 · 1 PDB

Full TAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MHC class I deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency by defective expression of MHC class I (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

TAP2 c.1636-1G>A Pathogenic/Likely pathogenic ★★ same condition
TAP2 c.1932+1G>A Uncertain significance ★★ same condition
TAP2 p.Ala17Val Uncertain significance ★★ ⚠ same condition
TAP2 p.Ala306Val Uncertain significance ★★ ⚠ same condition
TAP2 p.Ala500Thr Uncertain significance ★★ ⚠ same condition
TAP2 p.Ala500Val Uncertain significance ★★ ⚠ same condition
TAP2 p.Arg273Gln Uncertain significance ★★ ⚠ same condition
TAP2 p.Arg313Cys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tap2-p-val600 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown