Is TAP1 p.Phe591Ser (c.1772T>C) pathogenic?

TAP1 p.Phe591Ser (c.1772T>C) is classified Uncertain significance in TAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-02). AlphaMissense: ambiguous (0.3802); Very rare (popmax 0.00668%, afr); Associated with MHC class I deficiency.

What condition is associated with TAP1 p.Phe591Ser (c.1772T>C)?

TAP1 p.Phe591Ser (c.1772T>C) is associated with MHC class I deficiency (ClinVar).

How common is TAP1 p.Phe591Ser (c.1772T>C) in the general population?

TAP1 p.Phe591Ser (c.1772T>C) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about TAP1 p.Phe591Ser (c.1772T>C)?

AlphaMissense predicts ambiguous (score 0.3802) — an in-silico prediction, not a clinical call.

TAP1 p.Phe591Ser

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.1772T>C · rs994202939 · VCV852809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3802 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.3802	ambiguous
REVEL	0.912	moderately pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F651S vs ClinVar F591S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,816 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00031% 5/1,612,716 alleles · very rare

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.Phe591Ser
Coding: c.1772T>C
MANE Select: NM_000593
dbSNP: rs994202939
Type: single nucleotide variant
Location: chr6:32847644 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.03 · 22 PDB

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-phe591ser (accessed [today's date]).

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