Is TAP1 p.Ser4Phe (c.11C>T) pathogenic?

TAP1 p.Ser4Phe (c.11C>T) is classified Uncertain significance in TAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-02). AlphaMissense: likely benign (0.1336); Ultra-rare (popmax 0.0613%, afr); Associated with Inborn genetic diseases.

What condition is associated with TAP1 p.Ser4Phe (c.11C>T)?

TAP1 p.Ser4Phe (c.11C>T) is associated with Inborn genetic diseases, MHC class I deficiency (ClinVar).

How common is TAP1 p.Ser4Phe (c.11C>T) in the general population?

TAP1 p.Ser4Phe (c.11C>T) is ultra-rare (popmax 0.0613%, afr) (gnomAD).

What do computational predictors say about TAP1 p.Ser4Phe (c.11C>T)?

AlphaMissense predicts likely benign (score 0.1336) — an in-silico prediction, not a clinical call.

TAP1 p.Ser4Phe

c.11C>T · rs571573117 · VCV566325

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1336 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0613%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1336	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.2, phastCons 0.98
Overall
CADD	19.51	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S64F vs ClinVar S4F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0613% African / African-American · 46/75,046 alleles

Filtering AF 0.0471% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0422%

Overall 0.00316% 51/1,611,588 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0613%	1,631
Remaining individualsnot grpmax-eligible	0.00481%	20,807
Admixed American	0.00333%	29,990

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.Ser4Phe
Coding: c.11C>T
MANE Select: NM_000593
dbSNP: rs571573117
Type: single nucleotide variant
Location: chr6:32853626 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: MHC class I deficiency

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-ser4phe (accessed [today's date]).

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