Is RBFOX3 p.Pro13fs (c.35dup) pathogenic?

RBFOX3 p.Pro13fs (c.35dup) is classified Uncertain significance in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-17). No allele count reported in gnomAD v4.1 (AN 207,372); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro13fs (c.35dup)?

RBFOX3 p.Pro13fs (c.35dup) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro13fs (c.35dup) in the general population?

RBFOX3 p.Pro13fs (c.35dup) is no allele count reported in gnomAD v4.1 (AN 207,372) (gnomAD).

RBFOX3 p.Pro13fs

c.35dup · rs2510567398 · VCV2087324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 207,372)

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.72	GERP 0.61, phastCons 0.98

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 207,372). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RBFOX3
Protein: p.Pro13fs
Coding: c.35dup
MANE Select: NM_001350451
dbSNP: rs2510567398
Type: Duplication
Location: chr17:79115680 (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.Pro13= Likely benign ★ same residue
RBFOX3 p.Gly251fs Uncertain significance ★ same condition
RBFOX3 p.Tyr250Ter Uncertain significance ★ same condition
RBFOX3 c.508-7dup Likely benign ★ same condition
RBFOX3 c.622+3dup Benign ★ same condition
RBFOX3 c.998+13dup Benign ★ 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-pro13fs (accessed [today's date]).

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