Is RBFOX1 p.Pro46= (c.138C>T) pathogenic?

RBFOX1 p.Pro46= (c.138C>T) is classified Likely benign in RBFOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-11). Very rare (popmax 0.00424%, nfe); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX1 p.Pro46= (c.138C>T)?

RBFOX1 p.Pro46= (c.138C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX1 p.Pro46= (c.138C>T) in the general population?

RBFOX1 p.Pro46= (c.138C>T) is very rare (popmax 0.00424%, nfe) (gnomAD).

RBFOX1 p.Pro46=

c.138C>T · rs1315127050 · VCV1116429

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00424%, nfe)

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 -2.5	GERP -3.4
Overall
CADD	6.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00424% European (non-Finnish) · 50/1,180,006 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00328% 53/1,614,012 alleles · very rare exomes 51/1,461,840 · genomes 2/152,172 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00424%	23,600
Remaining individualsnot grpmax-eligible	0.0032%	31,240
African / African-American	0.00133%	74,936

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.Pro46=
Coding: c.138C>T
MANE Select: NM_018723
dbSNP: rs1315127050
Type: single nucleotide variant
Location: chr16:7518257 (GRCh38)
Gene constraint: LOEUF 0.311 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.23 · 4 PDB
Residue 46: 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.Pro46His Benign/Likely benign ★★ same residue
RBFOX1 p.Pro46Leu 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

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-pro46 (accessed [today's date]).

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