Is TRAF3 p.Pro18Arg (c.53C>G) pathogenic?

TRAF3 p.Pro18Arg (c.53C>G) is classified Uncertain significance in TRAF3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-12-29). AlphaMissense: likely benign (0.0919); Very rare (popmax 8.47e-05%, nfe); Associated with ependymoma.

What condition is associated with TRAF3 p.Pro18Arg (c.53C>G)?

TRAF3 p.Pro18Arg (c.53C>G) is associated with ependymoma (ClinVar).

How common is TRAF3 p.Pro18Arg (c.53C>G) in the general population?

TRAF3 p.Pro18Arg (c.53C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Ependymoma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TRAF3 p.Pro18Arg (c.53C>G)?

AlphaMissense predicts likely benign (score 0.0919) — an in-silico prediction, not a clinical call.

TRAF3 p.Pro18Arg

c.53C>G · rs145456077 · VCV487799

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ependymoma

Computational evidence

Protein change
AlphaMissense	0.0919	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -7.20	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 2.1	GERP 1, phastCons 0.94
Regional constraint	o/e 1.05	unconstrained · MANE · 84 bp · p 0.78 · regional, not allelic
Overall
CADD	10.56	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 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.2e-05% 1/1,614,186 alleles · very rare exomes 1/1,461,882 · genomes 0/152,304 · 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: TRAF3
Protein: p.Pro18Arg
Coding: c.53C>G
MANE Select: NM_145725
dbSNP: rs145456077
Type: single nucleotide variant
Location: chr14:102870254 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.26 · 10 PDB
Residue 18: the 'disordered' region

Full TRAF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ependymoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ependymoma (Orphanet):

Inheritance: Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

TRAF3 p.Pro18Leu Uncertain significance ★★ ⚠ same residue
TRAF3 p.Pro18= Likely benign ★ same residue
TRAF3 p.Trp344Ter Pathogenic ★★ same type
TRAF3 p.Ala188Val Uncertain significance ★★ ⚠ same type
TRAF3 p.Ala371Thr Uncertain significance ★★ ⚠ same type
TRAF3 p.Ala371Val Uncertain significance ★★ ⚠ same type
TRAF3 p.Ala78Val Uncertain significance ★★ ⚠ same type
TRAF3 p.Ala90Val 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/traf3-p-pro18arg (accessed [today's date]).

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