Is TAP1 p.Ala95Val (c.284C>T) pathogenic?

TAP1 p.Ala95Val (c.284C>T) is classified Conflicting classifications of pathogenicity in TAP1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-08-12). AlphaMissense: likely benign (0.0891); Very rare (popmax 0.00771%, nfe); Associated with MHC class I deficiency.

What condition is associated with TAP1 p.Ala95Val (c.284C>T)?

TAP1 p.Ala95Val (c.284C>T) is associated with MHC class I deficiency, MHC class I deficiency 1 (ClinVar).

How common is TAP1 p.Ala95Val (c.284C>T) in the general population?

TAP1 p.Ala95Val (c.284C>T) is very rare (popmax 0.00771%, nfe) (gnomAD).

What do computational predictors say about TAP1 p.Ala95Val (c.284C>T)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

TAP1 p.Ala95Val

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.284C>T · rs1383030445 · VCV1525487

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00771%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.182	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 2.1	GERP -0.65, phastCons 0.022
Overall
CADD	14.52	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 A155V vs ClinVar A95V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00771% European (non-Finnish) · 90/1,167,066 alleles

Filtering AF 0.00638% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0059%

Overall 0.00611% 97/1,587,714 alleles · very rare exomes 92/1,435,468 · genomes 5/152,246 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00771%	12,967
Remaining individualsnot grpmax-eligible	0.00488%	20,487
African / African-American	0.00403%	24,817
East Asian	0.00229%	43,686

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.Ala95Val
Coding: c.284C>T
MANE Select: NM_000593
dbSNP: rs1383030445
Type: single nucleotide variant
Location: chr6:32853353 (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

Also linked: MHC class I deficiency 1

For Immunodeficiency by defective expression of MHC class I (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

TAP1 p.Ala95Thr Uncertain significance ★ ⚠ same residue
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

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-ala95val (accessed [today's date]).

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