Is TAP1 p.Ala121= (c.363C>A) pathogenic?

TAP1 p.Ala121= (c.363C>A) is classified Likely benign in TAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). Very rare (popmax 0.00163%, nfe); Associated with MHC class I deficiency.

What condition is associated with TAP1 p.Ala121= (c.363C>A)?

TAP1 p.Ala121= (c.363C>A) is associated with MHC class I deficiency (ClinVar).

How common is TAP1 p.Ala121= (c.363C>A) in the general population?

TAP1 p.Ala121= (c.363C>A) is very rare (popmax 0.00163%, nfe) (gnomAD).

TAP1 p.Ala121=

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.363C>A · rs1275960530 · VCV1089578

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00163%, nfe)

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP -2.4
Overall
CADD	2.535	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00163% European (non-Finnish) · 19/1,166,294 alleles

Filtering AF 0.00104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00084%

Overall 0.00126% 20/1,587,564 alleles · very rare exomes 20/1,435,196 · genomes 0/152,368 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00163%	61,384
Remaining individualsnot grpmax-eligible	0.00163%	61,510

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: TAP1
Protein: p.Ala121=
Coding: c.363C>A
MANE Select: NM_000593
dbSNP: rs1275960530
Type: single nucleotide variant
Location: chr6:32853274 (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.Ala121Val Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ala121 (accessed [today's date]).

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