Is RBFOX3 p.Pro55Arg (c.164C>G) pathogenic?

RBFOX3 p.Pro55Arg (c.164C>G) is classified Uncertain significance in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-02). AlphaMissense: likely benign (0.116); Absent from gnomAD v4.1; Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro55Arg (c.164C>G)?

RBFOX3 p.Pro55Arg (c.164C>G) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro55Arg (c.164C>G) in the general population?

RBFOX3 p.Pro55Arg (c.164C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RBFOX3 p.Pro55Arg (c.164C>G)?

AlphaMissense predicts likely benign (score 0.116) — an in-silico prediction, not a clinical call.

RBFOX3 p.Pro55Arg

c.164C>G · rs2146997386 · VCV1494283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.116 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
AlphaMissense	0.116	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 8,995 bp · p 0.22 · regional, not allelic
Overall
CADD	23.8	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: RBFOX3
Protein: p.Pro55Arg
Coding: c.164C>G
MANE Select: NM_001350451
dbSNP: rs2146997386
Type: single nucleotide variant
Location: chr17:79115552 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27
Residue 55: the 'disordered' region

Full RBFOX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

idiopathic generalized epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBFOX3 p.Pro55Leu Uncertain significance ★ ⚠ same residue
RBFOX3 p.Pro55= Likely benign ★ same residue
RBFOX3 p.Ala316Thr Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala62Val Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala68Thr Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala79Val Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Ala8Thr Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Arg230Trp Uncertain significance ★★ ⚠ same condition

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/rbfox3-p-pro55arg (accessed [today's date]).

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