Is TRAF2 p.Ile285Val (c.853A>G) pathogenic?

TRAF2 p.Ile285Val (c.853A>G) is classified Uncertain significance in TRAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). AlphaMissense: ambiguous (0.4285); Very rare (popmax 0.00167%, amr).

How common is TRAF2 p.Ile285Val (c.853A>G) in the general population?

TRAF2 p.Ile285Val (c.853A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about TRAF2 p.Ile285Val (c.853A>G)?

AlphaMissense predicts ambiguous (score 0.4285) — an in-silico prediction, not a clinical call.

TRAF2 p.Ile285Val

c.853A>G · VCV3809943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4285	ambiguous
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.02	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Overall
CADD	21.4	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

Grpmax group 0.00167% Admixed American · 1/60,016 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,068 alleles · very rare exomes 6/1,461,828 · genomes 0/152,240 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,016
European (non-Finnish)	0.000424%	236,004

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: TRAF2
Protein: p.Ile285Val
Coding: c.853A>G
MANE Select: NM_021138
Type: single nucleotide variant
Location: chr9:136920408 (GRCh38)
Structure: AlphaFold pLDDT 60.31 · 3 PDB

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-ile285val (accessed [today's date]).

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