Is TRAF2 p.Arg150Cys (c.448C>T) pathogenic?

TRAF2 p.Arg150Cys (c.448C>T) is classified Uncertain significance in TRAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: likely benign (0.086); Ultra-rare (popmax 0.0747%, afr).

How common is TRAF2 p.Arg150Cys (c.448C>T) in the general population?

TRAF2 p.Arg150Cys (c.448C>T) is ultra-rare (popmax 0.0747%, afr) (gnomAD).

What do computational predictors say about TRAF2 p.Arg150Cys (c.448C>T)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

TRAF2 p.Arg150Cys

c.448C>T · rs373018887 · VCV2204132

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0747%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -10.39	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 4.7	GERP 1.2, phastCons 0.98
Overall
CADD	32.0	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 0.0747% African / African-American · 56/74,948 alleles

Filtering AF 0.059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0534%

Overall 0.00418% 67/1,604,222 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0747%	1,338
Remaining individualsnot grpmax-eligible	0.00481%	20,809
Admixed American	0.00333%	30,002
Finnishnot grpmax-eligible	0.00184%	54,344
South Asian	0.0011%	91,092
European (non-Finnish)	0.000339%	294,981

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.Arg150Cys
Coding: c.448C>T
MANE Select: NM_001199135 · reported on NM_021138
dbSNP: rs373018887
Type: single nucleotide variant
Location: chr9:136908151 (GRCh38)
Structure: AlphaFold pLDDT 60.31 · 3 PDB
Residue 150: 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.Arg150His Likely benign ★ 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-arg150cys (accessed [today's date]).

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