Is TAP2 p.Val387= (c.1161G>A) pathogenic?

TAP2 p.Val387= (c.1161G>A) is classified Benign in TAP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.85%, nfe); Associated with MHC class I deficiency.

What condition is associated with TAP2 p.Val387= (c.1161G>A)?

TAP2 p.Val387= (c.1161G>A) is associated with MHC class I deficiency (ClinVar).

How common is TAP2 p.Val387= (c.1161G>A) in the general population?

TAP2 p.Val387= (c.1161G>A) is low-frequency (popmax 2.85%, nfe) (gnomAD).

TAP2 p.Val387=

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.1161G>A · rs2856992 · VCV466365

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.85%, 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 0.94	GERP 0.92, phastCons 0.009
Overall
CADD	5.933	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.85% European (non-Finnish) · 33,662/1,179,844 alleles

Filtering AF 2.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.82%

Overall 2.39% 38,503/1,612,722 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	2.85%	35
Remaining individualsnot grpmax-eligible	2.23%	45
African / African-American	2.22%	45
Admixed American	2.19%	46
Amishnot grpmax-eligible	1.21%	83
Ashkenazi Jewishnot grpmax-eligible	0.747%	134
Middle Eastern	0.446%	224
Finnishnot grpmax-eligible	0.324%	309
South Asian	0.00879%	11,378
East Asian	0.00446%	22,442

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.Val387=
Coding: c.1161G>A
MANE Select: NM_001290043
dbSNP: rs2856992
Type: single nucleotide variant
Location: chr6:32832444 (GRCh38)
Structure: AlphaFold pLDDT 96.96 · 1 PDB
Residue 387: an α-helix

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 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.Ala306Val 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-val387 (accessed [today's date]).

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