Is TAP1 p.Thr331= (c.993C>G) pathogenic?

TAP1 p.Thr331= (c.993C>G) is classified Likely benign in TAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-09). Very rare (popmax 0.00167%, amr); Associated with MHC class I deficiency.

What condition is associated with TAP1 p.Thr331= (c.993C>G)?

TAP1 p.Thr331= (c.993C>G) is associated with MHC class I deficiency (ClinVar).

How common is TAP1 p.Thr331= (c.993C>G) in the general population?

TAP1 p.Thr331= (c.993C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

TAP1 p.Thr331=

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.993C>G · rs368862749 · VCV2977745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.41, phastCons 0.97
Overall
CADD	8.028	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000806% 13/1,612,788 alleles · very rare exomes 11/1,460,704 · genomes 2/152,084 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,478
South Asian	0.0011%	91,078
European (non-Finnish)	0.000847%	117,996

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: TAP1
Protein: p.Thr331=
Coding: c.993C>G
MANE Select: NM_000593
dbSNP: rs368862749
Type: single nucleotide variant
Location: chr6:32851001 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.03 · 22 PDB
Residue 331: the abc transmembrane type-1 domain; an α-helix

Full TAP1 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

TAP1 p.Arg378Ter Pathogenic ★★ same condition
TAP1 p.Gln522Ter Pathogenic/Likely pathogenic ★★ same condition
TAP1 c.-20G>C Uncertain significance ★★ ⚠ same condition
TAP1 c.-59C>T Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala101Val Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala2Thr Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala59Thr Uncertain significance ★★ ⚠ same condition
TAP1 p.Arg129Lys 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/tap1-p-thr331 (accessed [today's date]).

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