Is TAPBP p.Arg48Pro (c.143G>C) pathogenic?

TAPBP p.Arg48Pro (c.143G>C) is classified Uncertain significance in TAPBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: likely benign (0.2964); Very rare (popmax 8.47e-05%, nfe); Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Arg48Pro (c.143G>C)?

TAPBP p.Arg48Pro (c.143G>C) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Arg48Pro (c.143G>C) in the general population?

TAPBP p.Arg48Pro (c.143G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about TAPBP p.Arg48Pro (c.143G>C)?

AlphaMissense predicts likely benign (score 0.2964) — an in-silico prediction, not a clinical call.

TAPBP p.Arg48Pro

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.143G>C · VCV4773775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.2964	likely benign
REVEL	0.368	indeterminate
SaProt	LLR -9.38	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 5.4	GERP 1.6, phastCons 1
Overall
CADD	25.5	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.2e-05% 1/1,613,690 alleles · very rare exomes 1/1,461,452 · genomes 0/152,238 · joint denominator

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.Arg48Pro
Coding: c.143G>C
MANE Select: NM_003190
Type: single nucleotide variant
Location: chr6:33313759 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 12 PDB

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.Arg48Leu 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-arg48pro (accessed [today's date]).

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