Is TAPBP p.Phe427= (c.1281C>T) pathogenic?

TAPBP p.Phe427= (c.1281C>T) is classified Uncertain significance in TAPBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Absent from gnomAD v4.1; Associated with MHC class I deficiency.

What condition is associated with TAPBP p.Phe427= (c.1281C>T)?

TAPBP p.Phe427= (c.1281C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAPBP p.Phe427= (c.1281C>T) in the general population?

TAPBP p.Phe427= (c.1281C>T) is absent from gnomAD v4.1 (gnomAD).

TAPBP p.Phe427=

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.1281C>T · VCV3648465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.30	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 3.3	GERP -0.85, phastCons 1
Overall
CADD	2.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TAPBP
Protein: p.Phe427=
Coding: c.1281C>T
MANE Select: NM_003190
Type: single nucleotide variant
Location: chr6:33304147 (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.Phe427Leu 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-phe427 (accessed [today's date]).

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