Is RBFOX3 p.Pro13= (c.39G>A) pathogenic?

RBFOX3 p.Pro13= (c.39G>A) is classified Likely benign in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). Rare (popmax 0.136%, amr); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro13= (c.39G>A)?

RBFOX3 p.Pro13= (c.39G>A) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro13= (c.39G>A) in the general population?

RBFOX3 p.Pro13= (c.39G>A) is rare (popmax 0.136%, amr) (gnomAD).

RBFOX3 p.Pro13=

c.39G>A · rs940680437 · VCV1561390

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.136%, amr)

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 -20	GERP -3.1
Overall
CADD	3.321	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.136% Admixed American · 10/7,332 alleles

Filtering AF 0.0739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0563%

Overall 0.00616% 20/324,770 alleles · rare exomes 13/316,584 · genomes 7/8,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.136%	733
Remaining individualsnot grpmax-eligible	0.0343%	2,920
South Asian	0.0108%	9,260
European (non-Finnish)	0.00124%	80,717

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.Pro13=
Coding: c.39G>A
MANE Select: NM_001350451
dbSNP: rs940680437
Type: single nucleotide variant
Location: chr17:79115677 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27
Residue 13: 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.Pro13Arg Uncertain significance ★ same residue
RBFOX3 p.Pro13Leu Uncertain significance ★ ⚠ same residue
RBFOX3 p.Pro13fs 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

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-pro13 (accessed [today's date]).

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