Is TAPBP p.Ser395= (c.1185C>T) pathogenic?

TAPBP p.Ser395= (c.1185C>T) is classified Likely benign in TAPBP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). Ultra-rare (popmax 0.016%, afr); Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Ser395= (c.1185C>T)?

TAPBP p.Ser395= (c.1185C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Ser395= (c.1185C>T) in the general population?

TAPBP p.Ser395= (c.1185C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

TAPBP p.Ser395=

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.1185C>T · rs369975343 · VCV742719

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.093	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.7	GERP -3
Overall
CADD	0.245	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,888 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00349% 56/1,605,982 alleles · ultra-rare exomes 44/1,453,822 · genomes 12/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,241
East Asian	0.0112%	8,946
European (non-Finnish)	0.00315%	31,757
Admixed American	0.00168%	59,516
Remaining individualsnot grpmax-eligible	0.00161%	62,100

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.Ser395=
Coding: c.1185C>T
MANE Select: NM_003190
dbSNP: rs369975343
Type: single nucleotide variant
Location: chr6:33304322 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 12 PDB
Residue 395: the ig-like c1-type domain; 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.Ser395Arg 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-ser395 (accessed [today's date]).

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