Is RBFOX3 p.Pro55= (c.165C>T) pathogenic?

RBFOX3 p.Pro55= (c.165C>T) is classified Likely benign in RBFOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-24). Very rare (popmax 0.00153%, afr); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Pro55= (c.165C>T)?

RBFOX3 p.Pro55= (c.165C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Pro55= (c.165C>T) in the general population?

RBFOX3 p.Pro55= (c.165C>T) is very rare (popmax 0.00153%, afr) (gnomAD).

RBFOX3 p.Pro55=

c.165C>T · rs1019002644 · VCV1570650

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00153%, 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 -2.2	GERP -4.7
Overall
CADD	7.518	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% African / African-American · 1/65,388 alleles

Filtering AF 0.000207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000524% 7/1,335,540 alleles · very rare exomes 6/1,183,608 · genomes 1/151,932 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00153%	65,388
European (non-Finnish)	0.000577%	173,383

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.Pro55=
Coding: c.165C>T
MANE Select: NM_001350451
dbSNP: rs1019002644
Type: single nucleotide variant
Location: chr17:79115551 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27
Residue 55: 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.Pro55Arg Uncertain significance ★ ⚠ same residue
RBFOX3 p.Pro55Leu 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

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-pro55 (accessed [today's date]).

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