Is TRAF2 p.Ile197Phe (c.589A>T) pathogenic?

TRAF2 p.Ile197Phe (c.589A>T) is classified Uncertain significance in TRAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.3144); Absent from gnomAD v4.1.

How common is TRAF2 p.Ile197Phe (c.589A>T) in the general population?

TRAF2 p.Ile197Phe (c.589A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAF2 p.Ile197Phe (c.589A>T)?

AlphaMissense predicts likely benign (score 0.3144) — an in-silico prediction, not a clinical call.

TRAF2 p.Ile197Phe

c.589A>T · rs2491239564 · VCV2235207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3144 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3144	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -14.53	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.29, phastCons 1
Overall
CADD	20.9	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: TRAF2
Protein: p.Ile197Phe
Coding: c.589A>T
MANE Select: NM_021138
dbSNP: rs2491239564
Type: single nucleotide variant
Location: chr9:136909980 (GRCh38)
Structure: AlphaFold pLDDT 60.31 · 3 PDB
Residue 197: a functional site (cleavage by emcv protease 3c)

Full TRAF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TANK p.Gln113Glu Benign ★★ same type
TRAF2 p.Arg308= Benign ★★ same type
TRAF2 p.Gly81= Benign ★★ same type
TRAF2 p.Phe361= Benign ★★ same type
TANK p.Arg40Ser Uncertain significance ★ ⚠ same type
TANK p.Arg42Cys Uncertain significance ★ ⚠ same type
TANK p.Asn87Ser Uncertain significance ★ ⚠ same type
TANK p.Asn88Ile 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/traf2-p-ile197phe (accessed [today's date]).

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