Is TAP2 p.Val336Phe (c.1006G>T) pathogenic?

TAP2 p.Val336Phe (c.1006G>T) is classified Uncertain significance in TAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-09). AlphaMissense: likely benign (0.2264); Absent from gnomAD v4.1; Associated with MHC class I deficiency.

What condition is associated with TAP2 p.Val336Phe (c.1006G>T)?

TAP2 p.Val336Phe (c.1006G>T) is associated with MHC class I deficiency (ClinVar).

How common is TAP2 p.Val336Phe (c.1006G>T) in the general population?

TAP2 p.Val336Phe (c.1006G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TAP2 p.Val336Phe (c.1006G>T)?

AlphaMissense predicts likely benign (score 0.2264) — an in-silico prediction, not a clinical call.

TAP2 p.Val336Phe

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.1006G>T · rs1243600800 · VCV952167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2264 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,078)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.2264	likely benign
REVEL	0.597	indeterminate
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.12, phastCons 0.73
Overall
CADD	20.2	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,078). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TAP2
Protein: p.Val336Phe
Coding: c.1006G>T
MANE Select: NM_174975 · reported on NM_001290043
dbSNP: rs1243600800
Type: single nucleotide variant
Location: chr6:32832764 (GRCh38)
Structure: AlphaFold pLDDT 96.96 · 1 PDB
Residue 336: 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 p.Val336Ile Uncertain significance ★ ⚠ same residue
TAP2 p.Val336Ala Uncertain significance ★ ⚠ same residue
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

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-val336phe (accessed [today's date]).

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