Is TAPBP p.Ala219= (c.657T>G) pathogenic?

TAPBP p.Ala219= (c.657T>G) is classified Likely benign in TAPBP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). Very rare (popmax 8.47e-05%, nfe); Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Ala219= (c.657T>G)?

TAPBP p.Ala219= (c.657T>G) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Ala219= (c.657T>G) in the general population?

TAPBP p.Ala219= (c.657T>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TAPBP p.Ala219=

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.657T>G · rs994503210 · VCV1965184

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

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

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -1.7, phastCons 0.81
Overall
CADD	8.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,872 alleles · very rare

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.Ala219=
Coding: c.657T>G
MANE Select: NM_003190
dbSNP: rs994503210
Type: single nucleotide variant
Location: chr6:33305200 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 12 PDB
Residue 219: 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.Ala219fs Uncertain significance ★ same residue
TAPBP p.Ala219Thr 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

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-ala219 (accessed [today's date]).

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