Is TAPBP p.Pro197= (c.591G>A) pathogenic?

TAPBP p.Pro197= (c.591G>A) is classified Conflicting classifications of pathogenicity in TAPBP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-03). Rare (popmax 0.134%, mid); Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Pro197= (c.591G>A)?

TAPBP p.Pro197= (c.591G>A) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Pro197= (c.591G>A) in the general population?

TAPBP p.Pro197= (c.591G>A) is rare (popmax 0.134%, mid) (gnomAD).

TAPBP p.Pro197=

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.591G>A · rs200497341 · VCV626175

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.134%, mid)

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 -3.1	GERP -3.3
Overall
CADD	1.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% Middle Eastern · 8/5,986 alleles

Filtering AF 0.0665% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0485%

Overall 0.00724% 116/1,601,148 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.134%	748
Admixed American	0.0701%	1,427
Remaining individualsnot grpmax-eligible	0.0275%	3,638
African / African-American	0.0148%	6,778
South Asian	0.01%	9,993
European (non-Finnish)	0.00256%	39,079

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.Pro197=
Coding: c.591G>A
MANE Select: NM_003190
dbSNP: rs200497341
Type: single nucleotide variant
Location: chr6:33305266 (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.Pro197Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro197 (accessed [today's date]).

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