Is RBFOX1 p.Pro257= (c.771G>A) pathogenic?

RBFOX1 p.Pro257= (c.771G>A) is classified Likely benign in RBFOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-20). Very rare (popmax 0.00334%, amr); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX1 p.Pro257= (c.771G>A)?

RBFOX1 p.Pro257= (c.771G>A) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX1 p.Pro257= (c.771G>A) in the general population?

RBFOX1 p.Pro257= (c.771G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

RBFOX1 p.Pro257=

c.771G>A · rs916986800 · VCV699919

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, 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 -0.41	GERP -1.3, phastCons 0.004
Overall
CADD	10.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,966 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000684% 11/1,607,608 alleles · very rare exomes 9/1,455,548 · genomes 2/152,060 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,983
African / African-American	0.00134%	74,884
South Asian	0.0011%	91,060
European (non-Finnish)	0.000593%	168,505

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: RBFOX1
Protein: p.Pro257=
Coding: c.771G>A
MANE Select: NM_018723
dbSNP: rs916986800
Type: single nucleotide variant
Location: chr16:7653828 (GRCh38)
Gene constraint: LOEUF 0.311 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.23 · 4 PDB

Full RBFOX1 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

RBFOX1 p.Pro257Arg Uncertain significance ★ ⚠ same residue
RBFOX1 p.Ala21Ser Uncertain significance ★★ same condition
RBFOX1 p.Ala21Val Uncertain significance ★★ same condition
RBFOX1 p.Ala225Thr Uncertain significance ★★ ⚠ same condition
RBFOX1 p.Ala264Thr Uncertain significance ★★ ⚠ same condition
RBFOX1 p.Ala315Thr Uncertain significance ★★ ⚠ same condition
RBFOX1 p.Arg317Cys Uncertain significance ★★ ⚠ same condition
RBFOX1 p.Asn35Ser 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/rbfox1-p-pro257 (accessed [today's date]).

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