Is TAP2 p.Ser296Phe (c.887C>T) pathogenic?

TAP2 p.Ser296Phe (c.887C>T) is classified Uncertain significance in TAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-08). AlphaMissense: ambiguous (0.4205); Absent from gnomAD v4.1; Associated with MHC class I deficiency.

What condition is associated with TAP2 p.Ser296Phe (c.887C>T)?

TAP2 p.Ser296Phe (c.887C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAP2 p.Ser296Phe (c.887C>T) in the general population?

TAP2 p.Ser296Phe (c.887C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TAP2 p.Ser296Phe (c.887C>T)?

AlphaMissense predicts ambiguous (score 0.4205) — an in-silico prediction, not a clinical call.

TAP2 p.Ser296Phe

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.887C>T · rs1769335343 · VCV839788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4205 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.4205	ambiguous
REVEL	0.508	indeterminate
SaProt	LLR -10.54	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 1.4, phastCons 1
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TAP2
Protein: p.Ser296Phe
Coding: c.887C>T
MANE Select: NM_174975 · reported on NM_001290043
dbSNP: rs1769335343
Type: single nucleotide variant
Location: chr6:32835212 (GRCh38)
Structure: AlphaFold pLDDT 96.96 · 1 PDB
Residue 296: the gold domain; a β-strand

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-ser296phe (accessed [today's date]).

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