Is TAPBP p.Pro292= (c.876C>G) pathogenic?

TAPBP p.Pro292= (c.876C>G) is classified Likely benign in TAPBP (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-22). Ultra-rare (popmax 0.0501%, afr); Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Pro292= (c.876C>G)?

TAPBP p.Pro292= (c.876C>G) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Pro292= (c.876C>G) in the general population?

TAPBP p.Pro292= (c.876C>G) is ultra-rare (popmax 0.0501%, afr) (gnomAD).

TAPBP p.Pro292=

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.876C>G · rs555796568 · VCV1158789

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0501%, afr)

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.3	GERP -3.3
Overall
CADD	2.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0501% African / African-American · 37/73,854 alleles

Filtering AF 0.0373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0329%

Overall 0.00294% 46/1,565,730 alleles · ultra-rare exomes 22/1,413,486 · genomes 24/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0501%	1,996
Admixed American	0.00915%	10,930
Remaining individualsnot grpmax-eligible	0.00659%	15,175

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.Pro292=
Coding: c.876C>G
MANE Select: NM_003190
dbSNP: rs555796568
Type: single nucleotide variant
Location: chr6:33304631 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 12 PDB
Residue 292: the ig-like c1-type domain

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.Pro292Leu Uncertain significance ★ ⚠ same residue
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

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-pro292 (accessed [today's date]).

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