Is TAP1 p.Ser258Arg (c.774C>A) pathogenic?

TAP1 p.Ser258Arg (c.774C>A) is classified Uncertain significance in TAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-15). AlphaMissense: likely benign (0.256); Absent from gnomAD v4.1; Associated with MHC class I deficiency.

What condition is associated with TAP1 p.Ser258Arg (c.774C>A)?

TAP1 p.Ser258Arg (c.774C>A) is associated with MHC class I deficiency (ClinVar).

How common is TAP1 p.Ser258Arg (c.774C>A) in the general population?

TAP1 p.Ser258Arg (c.774C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TAP1 p.Ser258Arg (c.774C>A)?

AlphaMissense predicts likely benign (score 0.256) — an in-silico prediction, not a clinical call.

TAP1 p.Ser258Arg

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.774C>A · rs2127392345 · VCV1354600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.256 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.256	likely benign
REVEL	0.332	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.82, phastCons 1
Overall
CADD	19.65	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S318R vs ClinVar S258R) — verify the residue.

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: TAP1
Protein: p.Ser258Arg
Coding: c.774C>A
MANE Select: NM_000593
dbSNP: rs2127392345
Type: single nucleotide variant
Location: chr6:32852179 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.03 · 22 PDB

Full TAP1 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

TAP1 p.Arg378Ter Pathogenic ★★ same condition
TAP1 p.Gln522Ter Pathogenic/Likely pathogenic ★★ same condition
TAP1 c.-20G>C Uncertain significance ★★ ⚠ same condition
TAP1 c.-59C>T Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala101Val Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala2Thr Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala59Thr Uncertain significance ★★ ⚠ same condition
TAP1 p.Arg129Lys 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/tap1-p-ser258arg (accessed [today's date]).

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