Is TRRAP p.Ala1232Pro (c.3694G>C) pathogenic?

TRRAP p.Ala1232Pro (c.3694G>C) is classified Uncertain significance in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: ambiguous (0.3817); Absent from gnomAD v4.1.

How common is TRRAP p.Ala1232Pro (c.3694G>C) in the general population?

TRRAP p.Ala1232Pro (c.3694G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRRAP p.Ala1232Pro (c.3694G>C)?

AlphaMissense predicts ambiguous (score 0.3817) — an in-silico prediction, not a clinical call.

TRRAP p.Ala1232Pro

c.3694G>C · VCV4282173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3817 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3817	ambiguous
REVEL	0.107	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP -0.53, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,095 bp · p 2.8e-06 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ala1232Pro
Coding: c.3694G>C
MANE Select: NM_001375524
Type: single nucleotide variant
Location: chr7:98931507 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1232: an α-helix

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

Similar variants

TRRAP p.Ala1232= Likely benign ★★ same residue
TRRAP p.Ala1232Asp Uncertain significance ★ ⚠ same residue
TRRAP p.Ala1232Val 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

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-ala1232pro (accessed [today's date]).

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