Is TAP1 p.Pro137Arg (c.410C>G) pathogenic?

TAP1 p.Pro137Arg (c.410C>G) is classified Uncertain significance in TAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-03). AlphaMissense: likely benign (0.0995); Very rare (popmax 0.00801%, afr); Associated with MHC class I deficiency.

What condition is associated with TAP1 p.Pro137Arg (c.410C>G)?

TAP1 p.Pro137Arg (c.410C>G) is associated with MHC class I deficiency (ClinVar).

How common is TAP1 p.Pro137Arg (c.410C>G) in the general population?

TAP1 p.Pro137Arg (c.410C>G) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about TAP1 p.Pro137Arg (c.410C>G)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

TAP1 p.Pro137Arg

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.410C>G · rs1010241068 · VCV534705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.254	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 1.2	GERP -2.5, phastCons 0.2
Overall
CADD	6.191	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 P197R vs ClinVar P137R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,896 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000497% 8/1,609,410 alleles · very rare exomes 5/1,457,162 · genomes 3/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,483
Remaining individualsnot grpmax-eligible	0.0016%	62,326
European (non-Finnish)	8.49e-05%	1,178,300

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.Pro137Arg
Coding: c.410C>G
MANE Select: NM_000593
dbSNP: rs1010241068
Type: single nucleotide variant
Location: chr6:32853227 (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-pro137arg (accessed [today's date]).

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