Is TRAF2 p.His154Asp (c.460C>G) pathogenic?

TRAF2 p.His154Asp (c.460C>G) is classified Uncertain significance in TRAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.0937); Very rare (popmax 0.0011%, sas).

How common is TRAF2 p.His154Asp (c.460C>G) in the general population?

TRAF2 p.His154Asp (c.460C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about TRAF2 p.His154Asp (c.460C>G)?

AlphaMissense predicts likely benign (score 0.0937) — an in-silico prediction, not a clinical call.

TRAF2 p.His154Asp

c.460C>G · VCV3972814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0937 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0937	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.46	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 3.8	GERP -0.16, phastCons 1
Overall
CADD	19.08	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 6.24e-05% 1/1,602,974 alleles · very rare exomes 1/1,450,632 · genomes 0/152,342 · joint denominator

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.His154Asp
Coding: c.460C>G
MANE Select: NM_021138
Type: single nucleotide variant
Location: chr9:136908163 (GRCh38)
Structure: AlphaFold pLDDT 60.31 · 3 PDB
Residue 154: the 'necessary for interaction with traf6' region; the 'interaction with tbk1 and ikbke' region

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

Similar variants

TRAF2 p.His154Arg Uncertain significance ★ ⚠ same residue
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

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-his154asp (accessed [today's date]).

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