Is TAPBP p.Pro58Ser (c.172C>T) pathogenic?

TAPBP p.Pro58Ser (c.172C>T) is classified Likely benign in TAPBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0899); Rare (popmax 0.239%, sas); Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Pro58Ser (c.172C>T)?

TAPBP p.Pro58Ser (c.172C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Pro58Ser (c.172C>T) in the general population?

TAPBP p.Pro58Ser (c.172C>T) is rare (popmax 0.239%, sas) (gnomAD).

What do computational predictors say about TAPBP p.Pro58Ser (c.172C>T)?

AlphaMissense predicts likely benign (score 0.0899) — an in-silico prediction, not a clinical call.

TAPBP p.Pro58Ser

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.172C>T · rs376978188 · VCV1115132

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0899 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.239%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.0899	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -8.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -0.7, phastCons 1
Overall
CADD	17.15	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.239% South Asian · 218/91,064 alleles

Filtering AF 0.213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.203%

Overall 0.0202% 326/1,613,484 alleles · rare exomes 306/1,461,228 · genomes 20/152,256 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.239%	418
Middle Eastern	0.132%	758
Remaining individualsnot grpmax-eligible	0.0384%	2,604
European (non-Finnish)	0.00636%	15,733
African / African-American	0.00133%	75,030

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.Pro58Ser
Coding: c.172C>T
MANE Select: NM_003190
dbSNP: rs376978188
Type: single nucleotide variant
Location: chr6:33313730 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 12 PDB
Residue 58: 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.Pro58= Benign/Likely benign ★★ same residue
TAPBP p.Pro58Leu 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-pro58ser (accessed [today's date]).

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