Is TRRAP p.Pro2732Ala (c.8194C>G) pathogenic?

TRRAP p.Pro2732Ala (c.8194C>G) is classified Uncertain significance in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-25). AlphaMissense: likely benign (0.0928); Absent from gnomAD v4.1.

How common is TRRAP p.Pro2732Ala (c.8194C>G) in the general population?

TRRAP p.Pro2732Ala (c.8194C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRRAP p.Pro2732Ala (c.8194C>G)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

TRRAP p.Pro2732Ala

c.8194C>G · rs1792675459 · VCV2103347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 27 kb · p 6.5e-16 · regional, not allelic
Overall
CADD	22.9	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 P2725A vs ClinVar P2732A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRRAP
Protein: p.Pro2732Ala
Coding: c.8194C>G
MANE Select: NM_001375524
dbSNP: rs1792675459
Type: single nucleotide variant
Location: chr7:98976717 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

Full TRRAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRRAP p.Pro2732= Likely benign ★★ same residue
TRRAP p.Pro2732Leu Uncertain significance ★ ⚠ same residue
TRRAP p.Arg1035Gln Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Glu1104Gly Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Glu1106Lys Likely pathogenic ★★ same type
TRRAP p.Met3318Val Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Val1030Ile Likely pathogenic ★★ same type
TRRAP c.2622+3A>G Uncertain significance ★★ same type

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/trrap-p-pro2732ala (accessed [today's date]).

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