Is TRAF7 p.Arg653Trp (c.1957C>T) pathogenic?

TRAF7 p.Arg653Trp (c.1957C>T) is classified Uncertain significance in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-29). AlphaMissense: likely pathogenic (0.9225); Very rare (popmax 0.000509%, nfe).

How common is TRAF7 p.Arg653Trp (c.1957C>T) in the general population?

TRAF7 p.Arg653Trp (c.1957C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about TRAF7 p.Arg653Trp (c.1957C>T)?

AlphaMissense predicts likely pathogenic (score 0.9225) — an in-silico prediction, not a clinical call.

TRAF7 p.Arg653Trp

c.1957C>T · VCV4928078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9225 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9225	likely pathogenic
REVEL	0.403	indeterminate
SaProt	LLR -9.94	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 245 bp · p 0.12 · regional, not allelic
Overall
CADD	23.2	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 0.000509% European (non-Finnish) · 6/1,177,892 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000374% 6/1,604,472 alleles · very rare exomes 6/1,452,146 · genomes 0/152,326 · 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: TRAF7
Protein: p.Arg653Trp
Coding: c.1957C>T
MANE Select: NM_032271
Type: single nucleotide variant
Location: chr16:2176343 (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.Arg653Leu Likely pathogenic ★ ⚠ 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-arg653trp (accessed [today's date]).

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