Is RBFOX3 p.Pro38= (c.114G>A) pathogenic?

RBFOX3 p.Pro38= (c.114G>A) is classified Likely benign in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). Ultra-rare (popmax 0.0968%, eas); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro38= (c.114G>A)?

RBFOX3 p.Pro38= (c.114G>A) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro38= (c.114G>A) in the general population?

RBFOX3 p.Pro38= (c.114G>A) is ultra-rare (popmax 0.0968%, eas) (gnomAD).

RBFOX3 p.Pro38=

c.114G>A · rs372250322 · VCV695419

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0968%, 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 -8.6	GERP -4.7
Overall
CADD	6.474	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0968% East Asian · 17/17,570 alleles

Filtering AF 0.0616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0506%

Overall 0.0115% 140/1,219,330 alleles · ultra-rare exomes 127/1,086,914 · genomes 13/132,416 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0968%	1,034
Remaining individualsnot grpmax-eligible	0.0143%	7,005
European (non-Finnish)	0.0116%	8,619
African / African-American	0.00526%	18,999
Finnishnot grpmax-eligible	0.00349%	28,672
South Asian	0.00159%	62,764

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.Pro38=
Coding: c.114G>A
MANE Select: NM_001350451
dbSNP: rs372250322
Type: single nucleotide variant
Location: chr17:79115602 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27
Residue 38: 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.Pro38Leu 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-pro38 (accessed [today's date]).

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