Is TAPBP p.Ser392= (c.1176G>A) pathogenic?

TAPBP p.Ser392= (c.1176G>A) is classified Likely benign in TAPBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-27). Very rare (popmax 0.00357%, nfe); Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Ser392= (c.1176G>A)?

TAPBP p.Ser392= (c.1176G>A) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Ser392= (c.1176G>A) in the general population?

TAPBP p.Ser392= (c.1176G>A) is very rare (popmax 0.00357%, nfe) (gnomAD).

TAPBP p.Ser392=

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.1176G>A · rs768859558 · VCV2192971

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00357%, nfe)

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.016	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -3
Overall
CADD	0.968	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00357% European (non-Finnish) · 42/1,175,788 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00237%

Overall 0.0028% 45/1,607,206 alleles · very rare exomes 41/1,455,138 · genomes 4/152,068 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00357%	27,995
Finnishnot grpmax-eligible	0.00157%	63,816
African / African-American	0.00134%	74,790
South Asian	0.00111%	90,352

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.Ser392=
Coding: c.1176G>A
MANE Select: NM_003190
dbSNP: rs768859558
Type: single nucleotide variant
Location: chr6:33304331 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 12 PDB
Residue 392: the ig-like c1-type domain

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.Ser392Leu 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-ser392 (accessed [today's date]).

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