Is TAP1 p.Pro172Arg (c.515C>G) pathogenic?

TAP1 p.Pro172Arg (c.515C>G) is classified Uncertain significance in TAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). AlphaMissense: likely benign (0.0823); Very rare (popmax 0.000847%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TAP1 p.Pro172Arg (c.515C>G)?

TAP1 p.Pro172Arg (c.515C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TAP1 p.Pro172Arg (c.515C>G) in the general population?

TAP1 p.Pro172Arg (c.515C>G) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about TAP1 p.Pro172Arg (c.515C>G)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

TAP1 p.Pro172Arg

c.515C>G · VCV4632655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.065	GERP -2.8
Overall
CADD	6.112	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P232R vs ClinVar P172R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000847% European (non-Finnish) · 10/1,180,000 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000868% 14/1,612,726 alleles · very rare exomes 13/1,460,492 · genomes 1/152,234 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00641%	15,609
European (non-Finnish)grpmax	0.000847%	118,000

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: TAP1
Protein: p.Pro172Arg
Coding: c.515C>G
MANE Select: NM_000593
Type: single nucleotide variant
Location: chr6:32853122 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TAP1 c.-20G>C Uncertain significance ★★ ⚠ same condition
TAP1 c.-59C>T Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala2Thr Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala59Thr Uncertain significance ★★ ⚠ same condition
TAP1 p.Arg129Lys Uncertain significance ★★ ⚠ same condition
TAP1 p.Arg575Cys Uncertain significance ★★ ⚠ same condition
TAP1 p.Arg659Trp Uncertain significance ★★ ⚠ same condition
TAP1 p.Asn401Lys 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-pro172arg (accessed [today's date]).

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