Is TAPBP p.Pro310Ser (c.928C>T) pathogenic?

TAPBP p.Pro310Ser (c.928C>T) is classified Uncertain significance in TAPBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-20). AlphaMissense: likely benign (0.2079); Ultra-rare (popmax 0.0134%, amr); Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Pro310Ser (c.928C>T)?

TAPBP p.Pro310Ser (c.928C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Pro310Ser (c.928C>T) in the general population?

TAPBP p.Pro310Ser (c.928C>T) is ultra-rare (popmax 0.0134%, amr) (gnomAD).

What do computational predictors say about TAPBP p.Pro310Ser (c.928C>T)?

AlphaMissense predicts likely benign (score 0.2079) — an in-silico prediction, not a clinical call.

TAPBP p.Pro310Ser

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.928C>T · rs750393786 · VCV965843

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2079 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.2079	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.7, phastCons 1
Overall
CADD	21.9	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

Grpmax group 0.0134% Admixed American · 8/59,516 alleles

Filtering AF 0.00666% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00486%

Overall 0.00237% 38/1,603,226 alleles · ultra-rare exomes 33/1,451,060 · genomes 5/152,166 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0134%	7,439
Ashkenazi Jewishnot grpmax-eligible	0.00679%	14,721
Finnishnot grpmax-eligible	0.0054%	18,515
Remaining individualsnot grpmax-eligible	0.00481%	20,775
European (non-Finnish)	0.00178%	56,132
African / African-American	0.00134%	74,820

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: TAPBP
Protein: p.Pro310Ser
Coding: c.928C>T
MANE Select: NM_003190
dbSNP: rs750393786
Type: single nucleotide variant
Location: chr6:33304579 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 12 PDB
Residue 310: the ig-like c1-type domain; an α-helix

Full TAPBP 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

TAPBP p.Ala191Thr Uncertain significance ★★ ⚠ same condition
TAPBP p.Ala220Val Uncertain significance ★★ ⚠ same condition
TAPBP p.Ala305Ser Uncertain significance ★★ ⚠ same condition
TAPBP p.Ala305Thr Uncertain significance ★★ ⚠ same condition
TAPBP p.Ala309Glu Uncertain significance ★★ ⚠ same condition
TAPBP p.Ala396Thr Uncertain significance ★★ ⚠ same condition
TAPBP p.Ala433Thr Uncertain significance ★★ ⚠ same condition
TAPBP p.Arg208Cys 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/tapbp-p-pro310ser (accessed [today's date]).

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