Is RBFOX3 p.Pro245= (c.735C>G) pathogenic?

RBFOX3 p.Pro245= (c.735C>G) is classified Likely benign in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-03). Ultra-rare (popmax 0.0157%, nfe); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro245= (c.735C>G)?

RBFOX3 p.Pro245= (c.735C>G) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro245= (c.735C>G) in the general population?

RBFOX3 p.Pro245= (c.735C>G) is ultra-rare (popmax 0.0157%, nfe) (gnomAD).

RBFOX3 p.Pro245=

c.735C>G · rs911540420 · VCV1631693

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, nfe)

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP -2.1, phastCons 1
Overall
CADD	10.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0157% European (non-Finnish) · 180/1,143,680 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.013% 201/1,544,838 alleles · ultra-rare exomes 192/1,392,810 · genomes 9/152,028 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0157%	6,354
Admixed American	0.0118%	8,441
Finnishnot grpmax-eligible	0.0103%	9,723
Remaining individualsnot grpmax-eligible	0.01%	9,960
African / African-American	0.00412%	24,275

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: RBFOX3
Protein: p.Pro245=
Coding: c.735C>G
MANE Select: NM_001350451
dbSNP: rs911540420
Type: single nucleotide variant
Location: chr17:79097312 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27

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.Pro245Ser Uncertain significance ★ ⚠ 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
RBFOX3 p.Gln31Arg 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-pro245 (accessed [today's date]).

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