Is TAP2 p.Pro8= (c.24C>T) pathogenic?

TAP2 p.Pro8= (c.24C>T) is classified Likely benign in TAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). Ultra-rare (popmax 0.0135%, eas); Associated with MHC class I deficiency.

What condition is associated with TAP2 p.Pro8= (c.24C>T)?

TAP2 p.Pro8= (c.24C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAP2 p.Pro8= (c.24C>T) in the general population?

TAP2 p.Pro8= (c.24C>T) is ultra-rare (popmax 0.0135%, eas) (gnomAD).

TAP2 p.Pro8=

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.24C>T · VCV4749215

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, eas)

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 1.1	GERP 1.6, phastCons 1
Overall
CADD	10.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% East Asian · 6/44,598 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.000631% 10/1,585,258 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0135%	7,433
Remaining individualsnot grpmax-eligible	0.00164%	61,148
European (non-Finnish)	0.000257%	389,022

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.Pro8=
Coding: c.24C>T
MANE Select: NM_174975 · reported on NM_001290043
Type: single nucleotide variant
Location: chr6:32838210 (GRCh38)
Structure: AlphaFold pLDDT 96.96 · 1 PDB

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-pro8 (accessed [today's date]).

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