Is RBFOX3 p.Pro24= (c.72G>A) pathogenic?

RBFOX3 p.Pro24= (c.72G>A) is classified Likely benign in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-21). Rare (popmax 0.281%, eas); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro24= (c.72G>A)?

RBFOX3 p.Pro24= (c.72G>A) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro24= (c.72G>A) in the general population?

RBFOX3 p.Pro24= (c.72G>A) is rare (popmax 0.281%, eas) (gnomAD).

RBFOX3 p.Pro24=

c.72G>A · rs776796401 · VCV1123204

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.281%, 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 -14	GERP -4.7
Overall
CADD	2.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.281% East Asian · 33/11,738 alleles

Filtering AF 0.206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.18%

Overall 0.0093% 91/978,052 alleles · rare exomes 80/918,860 · genomes 11/59,192 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.281%	356
Admixed American	0.0379%	2,639
Finnishnot grpmax-eligible	0.00791%	12,640
Remaining individualsnot grpmax-eligible	0.00591%	16,908
European (non-Finnish)	0.0058%	17,247
African / African-American	0.00305%	32,790
South Asian	0.00219%	45,694

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.Pro24=
Coding: c.72G>A
MANE Select: NM_001350451
dbSNP: rs776796401
Type: single nucleotide variant
Location: chr17:79115644 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27
Residue 24: 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.Pro24Leu 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-pro24 (accessed [today's date]).

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