Is RBFOX3 p.Pro343= (c.1029G>A) pathogenic?

RBFOX3 p.Pro343= (c.1029G>A) is classified Likely benign in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Ultra-rare (popmax 0.0264%, eas); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro343= (c.1029G>A)?

RBFOX3 p.Pro343= (c.1029G>A) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro343= (c.1029G>A) in the general population?

RBFOX3 p.Pro343= (c.1029G>A) is ultra-rare (popmax 0.0264%, eas) (gnomAD).

RBFOX3 p.Pro343=

c.1029G>A · rs373093807 · VCV460025

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, eas)

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 0.52	GERP -2, phastCons 0.99
Overall
CADD	13.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0264% East Asian · 3/11,350 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.00735% 90/1,224,350 alleles · ultra-rare exomes 78/1,088,856 · genomes 12/135,494 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0264%	3,783
African / African-American	0.0232%	4,314
European (non-Finnish)	0.00728%	13,742
Remaining individualsnot grpmax-eligible	0.00484%	20,644
South Asian	0.00283%	35,392

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.Pro343=
Coding: c.1029G>A
MANE Select: NM_001350451
dbSNP: rs373093807
Type: single nucleotide variant
Location: chr17:79094499 (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.Pro343Arg Uncertain significance ★ same residue
RBFOX3 p.Pro343Leu 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

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-pro343 (accessed [today's date]).

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