Is TAP1 p.Arg691Pro (c.2072G>C) pathogenic?

TAP1 p.Arg691Pro (c.2072G>C) is classified Uncertain significance in TAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-07). AlphaMissense: likely benign (0.2325); Ultra-rare (popmax 0.0188%, nfe); Associated with MHC class I deficiency.

What condition is associated with TAP1 p.Arg691Pro (c.2072G>C)?

TAP1 p.Arg691Pro (c.2072G>C) is associated with MHC class I deficiency (ClinVar).

How common is TAP1 p.Arg691Pro (c.2072G>C) in the general population?

TAP1 p.Arg691Pro (c.2072G>C) is ultra-rare (popmax 0.0188%, nfe) (gnomAD).

What do computational predictors say about TAP1 p.Arg691Pro (c.2072G>C)?

AlphaMissense predicts likely benign (score 0.2325) — an in-silico prediction, not a clinical call.

TAP1 p.Arg691Pro

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.2072G>C · rs200753447 · VCV972503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2325 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, nfe)

Conditions

MHC class I deficiency

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2325	likely benign
REVEL	0.568	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.12	GERP -1.2
Regional constraint	o/e 0.80	unconstrained · MANE · 3,193 bp · p 0.00027 · regional, not allelic
Overall
CADD	16.66	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R751P vs ClinVar R691P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0188% European (non-Finnish) · 222/1,180,008 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.0153% 247/1,612,566 alleles · ultra-rare exomes 230/1,460,384 · genomes 17/152,182 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,742
European (non-Finnish)grpmax	0.0188%	5,315
Remaining individualsnot grpmax-eligible	0.00961%	10,411
African / African-American	0.00267%	37,462

Ashkenazi Jewish 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: TAP1
Protein: p.Arg691Pro
Coding: c.2072G>C
MANE Select: NM_000593
dbSNP: rs200753447
Type: single nucleotide variant
Location: chr6:32845754 (GRCh38)

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

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-arg691pro (accessed [today's date]).

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