Is RBFOX1 p.Pro25= (c.75T>C) pathogenic?

RBFOX1 p.Pro25= (c.75T>C) is classified Likely benign in RBFOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). Absent from gnomAD v4.1; Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX1 p.Pro25= (c.75T>C)?

RBFOX1 p.Pro25= (c.75T>C) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX1 p.Pro25= (c.75T>C) in the general population?

RBFOX1 p.Pro25= (c.75T>C) is absent from gnomAD v4.1 (gnomAD).

RBFOX1 p.Pro25=

c.75T>C · rs2144461588 · VCV1157321

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.54	GERP -5.4, phastCons 0.016
Overall
CADD	9.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RBFOX1
Protein: p.Pro25=
Coding: c.75T>C
MANE Select: NM_018723 · reported on NM_145893
dbSNP: rs2144461588
Type: single nucleotide variant
Location: chr16:7333076 (GRCh38)
Gene constraint: LOEUF 0.311 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.23 · 4 PDB
Residue 25: the 'disordered' region

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.Pro25Leu 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-pro25 (accessed [today's date]).

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