Is TAP2 p.Ala306= (c.918G>A) pathogenic?

TAP2 p.Ala306= (c.918G>A) is classified Benign in TAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Rare (popmax 0.862%, sas); Associated with MHC class I deficiency.

What condition is associated with TAP2 p.Ala306= (c.918G>A)?

TAP2 p.Ala306= (c.918G>A) is associated with MHC class I deficiency (ClinVar).

How common is TAP2 p.Ala306= (c.918G>A) in the general population?

TAP2 p.Ala306= (c.918G>A) is rare (popmax 0.862%, sas) (gnomAD).

TAP2 p.Ala306=

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.918G>A · rs556799828 · VCV466375

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.862%, sas)

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 -4.6	GERP -2.9
Overall
CADD	0.248	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.862% South Asian · 785/91,074 alleles

Filtering AF 0.812% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.792%

Overall 0.0549% 886/1,612,920 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.862%	116
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Middle Eastern	0.0168%	5,952
European (non-Finnish)	0.00449%	22,265
East Asian	0.00446%	22,442
African / African-American	0.00267%	37,509
Admixed American	0.00167%	60,032

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: TAP2
Protein: p.Ala306=
Coding: c.918G>A
MANE Select: NM_174975 · reported on NM_001290043
dbSNP: rs556799828
Type: single nucleotide variant
Location: chr6:32835181 (GRCh38)
Structure: AlphaFold pLDDT 96.96 · 1 PDB
Residue 306: the gold domain; a β-strand

Full TAP2 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

TAP2 p.Ala306Val Uncertain significance ★★ ⚠ same residue
TAP2 c.1636-1G>A Pathogenic/Likely pathogenic ★★ same condition
TAP2 c.1932+1G>A Uncertain significance ★★ same condition
TAP2 p.Ala17Val Uncertain significance ★★ ⚠ same condition
TAP2 p.Ala500Thr Uncertain significance ★★ ⚠ same condition
TAP2 p.Ala500Val Uncertain significance ★★ ⚠ same condition
TAP2 p.Arg273Gln Uncertain significance ★★ ⚠ same condition
TAP2 p.Arg313Cys 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/tap2-p-ala306 (accessed [today's date]).

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