Is TAPBP p.Ser413= (c.1239C>T) pathogenic?

TAPBP p.Ser413= (c.1239C>T) is classified Benign in TAPBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 12.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Ser413= (c.1239C>T)?

TAPBP p.Ser413= (c.1239C>T) is associated with MHC class I deficiency (ClinVar).

TAPBP p.Ser413=

Q: How common is TAPBP p.Ser413= (c.1239C>T) in the general population?

TAPBP p.Ser413= (c.1239C>T) is common (popmax 12.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.1239C>T · rs34132052 · VCV466396

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 12.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing
Pangolin	Δ0.23	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -2.6	GERP -2.9
Overall
CADD	1.669	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.1% African / African-American · 9,063/74,818 alleles

Filtering AF 11.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.8%

Overall 0.647% 10,447/1,613,574 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.1%	8
Middle Eastern	0.841%	119
Remaining individualsnot grpmax-eligible	0.768%	130
Admixed American	0.729%	137
South Asian	0.126%	792
European (non-Finnish)	0.0255%	3,920

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.Ser413=
Coding: c.1239C>T
MANE Select: NM_003190
dbSNP: rs34132052
Type: single nucleotide variant
Location: chr6:33304189 (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.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
TAPBP p.Arg208Cys 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-ser413 (accessed [today's date]).

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