Is TRAF3IP2 p.Ala293Pro (c.877G>C) pathogenic?

TRAF3IP2 p.Ala293Pro (c.877G>C) is classified Uncertain significance in TRAF3IP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-08). AlphaMissense: likely benign (0.0969); Absent from gnomAD v4.1.

How common is TRAF3IP2 p.Ala293Pro (c.877G>C) in the general population?

TRAF3IP2 p.Ala293Pro (c.877G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAF3IP2 p.Ala293Pro (c.877G>C)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

TRAF3IP2 p.Ala293Pro

c.877G>C · VCV4189786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -5.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.93, phastCons 0.99
Regional constraint	o/e 0.86	unconstrained · MANE · 19 kb · p 0.0015 · regional, not allelic
Overall
CADD	20.6	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 and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A302P vs ClinVar A293P) — 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: TRAF3IP2
Protein: p.Ala293Pro
Coding: c.877G>C
MANE Select: NM_147686
Type: single nucleotide variant
Location: chr6:111580342 (GRCh38)
Gene constraint: LOEUF 0.771 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.91 · 1 PDB

Full TRAF3IP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAF3IP2 p.Ala293Gly Uncertain significance ★ ⚠ same residue
TRAF3IP2 c.1201+1G>C Likely pathogenic ★★ same type
TRAF3IP2 p.Ala328Thr Uncertain significance ★★ ⚠ same type
TRAF3IP2 p.Ala36Val Uncertain significance ★★ ⚠ same type
TRAF3IP2 p.Ala473Thr Uncertain significance ★★ ⚠ same type
TRAF3IP2 p.Asn45Lys Uncertain significance ★★ ⚠ same type
TRAF3IP2 p.Gln18His Uncertain significance ★★ ⚠ same type
TRAF3IP2 p.Glu479Lys 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/traf3ip2-p-ala293pro (accessed [today's date]).

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