Is TAP2 p.Pro504= (c.1512C>T) pathogenic?

TAP2 p.Pro504= (c.1512C>T) is classified Likely benign in TAP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-08). Very rare (popmax 0.00593%, nfe); Associated with MHC class I deficiency.

What condition is associated with TAP2 p.Pro504= (c.1512C>T)?

TAP2 p.Pro504= (c.1512C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAP2 p.Pro504= (c.1512C>T) in the general population?

TAP2 p.Pro504= (c.1512C>T) is very rare (popmax 0.00593%, nfe) (gnomAD).

TAP2 p.Pro504=

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.1512C>T · rs750188023 · VCV1142653

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00593%, 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 2.9	GERP 1.9, phastCons 1
Overall
CADD	12.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00593% European (non-Finnish) · 70/1,180,036 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00465% 75/1,612,954 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,618
European (non-Finnish)grpmax	0.00593%	16,858
South Asian	0.0011%	91,090

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro504=
Coding: c.1512C>T
MANE Select: NM_174975 · reported on NM_001290043
dbSNP: rs750188023
Type: single nucleotide variant
Location: chr6:32830390 (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 p.Pro504His 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.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

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-pro504 (accessed [today's date]).

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