Is TAP1 p.Ala146= (c.438G>A) pathogenic?

TAP1 p.Ala146= (c.438G>A) is classified Benign in TAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-23). Low-frequency (popmax 2.37%, sas); Associated with MHC class I deficiency.

What condition is associated with TAP1 p.Ala146= (c.438G>A)?

TAP1 p.Ala146= (c.438G>A) is associated with MHC class I deficiency (ClinVar).

How common is TAP1 p.Ala146= (c.438G>A) in the general population?

TAP1 p.Ala146= (c.438G>A) is low-frequency (popmax 2.37%, sas) (gnomAD).

TAP1 p.Ala146=

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.438G>A · rs78410191 · VCV466390

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.37%, 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 -3.9	GERP -2.5
Overall
CADD	4.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.37% South Asian · 2,152/90,878 alleles

Filtering AF 2.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.25%

Overall 0.196% 3,152/1,612,170 alleles · low-frequency exomes 2,784/1,459,838 · genomes 368/152,332 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.37%	42
African / African-American	0.584%	171
Remaining individualsnot grpmax-eligible	0.207%	484
Middle Eastern	0.165%	606
Admixed American	0.0784%	1,275
European (non-Finnish)	0.0311%	3,214
East Asian	0.0201%	4,986

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.Ala146=
Coding: c.438G>A
MANE Select: NM_000593
dbSNP: rs78410191
Type: single nucleotide variant
Location: chr6:32853199 (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.Ala146Val Benign/Likely benign ★★ 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-ala146 (accessed [today's date]).

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