Is TRAF7 p.Arg232Trp (c.694C>T) pathogenic?

TRAF7 p.Arg232Trp (c.694C>T) is classified Likely benign in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-01). AlphaMissense: likely benign (0.2254); Ultra-rare (popmax 0.0112%, eas).

How common is TRAF7 p.Arg232Trp (c.694C>T) in the general population?

TRAF7 p.Arg232Trp (c.694C>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about TRAF7 p.Arg232Trp (c.694C>T)?

AlphaMissense predicts likely benign (score 0.2254) — an in-silico prediction, not a clinical call.

TRAF7 p.Arg232Trp

c.694C>T · VCV4873271

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2254 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2254	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -10.90	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 2,613 bp · p 1e-09 · regional, not allelic
Overall
CADD	33.0	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 0.0112% East Asian · 5/44,654 alleles

Filtering AF 0.00436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00277%

Overall 0.00168% 27/1,606,642 alleles · ultra-rare exomes 24/1,454,438 · genomes 3/152,204 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,931
South Asian	0.00556%	17,988
African / African-American	0.00267%	37,410
Remaining individualsnot grpmax-eligible	0.00161%	62,168
European (non-Finnish)	0.00119%	84,115

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: TRAF7
Protein: p.Arg232Trp
Coding: c.694C>T
MANE Select: NM_032271
Type: single nucleotide variant
Location: chr16:2172499 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 1 PDB

Full TRAF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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TRAF7 p.Leu625Val Pathogenic/Likely pathogenic ★★ ⚠ same type
TRAF7 p.Ser558Phe Pathogenic ★★ ⚠ same type
TRAF7 p.Ser629Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
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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/traf7-p-arg232trp (accessed [today's date]).

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