Is TRAF7 p.Arg229Ser (c.687G>C) pathogenic?

TRAF7 p.Arg229Ser (c.687G>C) is classified Uncertain significance in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-30). AlphaMissense: ambiguous (0.4642); Absent from gnomAD v4.1.

How common is TRAF7 p.Arg229Ser (c.687G>C) in the general population?

TRAF7 p.Arg229Ser (c.687G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAF7 p.Arg229Ser (c.687G>C)?

AlphaMissense predicts ambiguous (score 0.4642) — an in-silico prediction, not a clinical call.

TRAF7 p.Arg229Ser

c.687G>C · rs760492852 · VCV2582097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4642 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4642	ambiguous
REVEL	0.185	benign-leaning
SaProt	LLR -4.79	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 1.4	GERP -2, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 2,613 bp · p 1e-09 · regional, not allelic
Overall
CADD	18.77	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: TRAF7
Protein: p.Arg229Ser
Coding: c.687G>C
MANE Select: NM_032271
dbSNP: rs760492852
Type: single nucleotide variant
Location: chr16:2172492 (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

TRAF7 p.Arg229= Likely benign ★ same residue
TRAF7 p.Arg524Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
TRAF7 p.Arg655Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
TRAF7 p.Leu402Val Pathogenic ★★ ⚠ same type
TRAF7 p.Leu625Val Pathogenic/Likely pathogenic ★★ ⚠ same type
TRAF7 p.Ser558Phe Pathogenic ★★ ⚠ same type
TRAF7 p.Ser629Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
TRAF7 p.Arg316Cys 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/traf7-p-arg229ser (accessed [today's date]).

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