Is RBFOX3 p.Pro7= (c.21C>T) pathogenic?

RBFOX3 p.Pro7= (c.21C>T) is classified Likely benign in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-27). Ultra-rare (popmax 0.0158%, afr); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro7= (c.21C>T)?

RBFOX3 p.Pro7= (c.21C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro7= (c.21C>T) in the general population?

RBFOX3 p.Pro7= (c.21C>T) is ultra-rare (popmax 0.0158%, afr) (gnomAD).

RBFOX3 p.Pro7=

c.21C>T · rs751793355 · VCV1144695

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, afr)

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	4.802	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0158% African / African-American · 9/57,028 alleles

Filtering AF 0.0082% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00615%

Overall 0.00385% 31/805,856 alleles · ultra-rare exomes 20/654,156 · genomes 11/151,700 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0158%	6,336
European (non-Finnish)	0.00365%	27,410
Remaining individualsnot grpmax-eligible	0.00299%	33,428
Finnishnot grpmax-eligible	0.00262%	38,104
Admixed American	0.00243%	41,152

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.Pro7=
Coding: c.21C>T
MANE Select: NM_001350451
dbSNP: rs751793355
Type: single nucleotide variant
Location: chr17:79115695 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27
Residue 7: 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.Pro7Leu Uncertain significance ★ ⚠ same residue
RBFOX3 p.Pro7Ser Conflicting classifications of pathogenicity ★ ⚠ 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

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-pro7 (accessed [today's date]).

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