Is TAPBP p.Val282fs (c.845del) pathogenic?

TAPBP p.Val282fs (c.845del) is classified Uncertain significance in TAPBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-13). Very rare (popmax 0.0061%, nfe); Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Val282fs (c.845del)?

TAPBP p.Val282fs (c.845del) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Val282fs (c.845del) in the general population?

TAPBP p.Val282fs (c.845del) is very rare (popmax 0.0061%, nfe) (gnomAD).

TAPBP p.Val282fs

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.845del · rs765712832 · VCV534706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0061%, nfe)

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.6	GERP -2.2, phastCons 0.32
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0061% European (non-Finnish) · 72/1,180,032 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00465% 75/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0061%	16,389
African / African-American	0.00267%	37,466
Admixed American	0.00167%	60,000

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.Val282fs
Coding: c.845del
MANE Select: NM_003190
dbSNP: rs765712832
Type: Deletion
Location: chr6:33305012 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 12 PDB
Residue 282: a β-strand

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.Val282Phe Uncertain significance ★ ⚠ same residue
TAPBP c.130_470-3608del Uncertain significance ★ same condition
TAPBP c.1300+3_1300+6del Uncertain significance ★ same condition
TAPBP c.1335+4_1335+5del Uncertain significance ★ same condition
TAPBP p.Ala219fs Uncertain significance ★ same condition
TAPBP p.Asp32fs Uncertain significance ★ same condition
TAPBP p.Cys440fs Uncertain significance ★ same condition
TAPBP p.Glu190fs 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-val282fs (accessed [today's date]).

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