Is RBFOX3 p.Phe145= (c.435T>C) pathogenic?

RBFOX3 p.Phe145= (c.435T>C) is classified Likely benign in RBFOX3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-05). Very rare (popmax 0.000174%, nfe); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX3 p.Phe145= (c.435T>C)?

RBFOX3 p.Phe145= (c.435T>C) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX3 p.Phe145= (c.435T>C) in the general population?

RBFOX3 p.Phe145= (c.435T>C) is very rare (popmax 0.000174%, nfe) (gnomAD).

RBFOX3 p.Phe145=

c.435T>C · rs754135050 · VCV1574851

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

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 6.8	GERP -2.8, phastCons 1
Overall
CADD	13.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,146,870 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000129% 2/1,551,288 alleles · very rare exomes 2/1,399,032 · genomes 0/152,256 · joint denominator

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.Phe145=
Coding: c.435T>C
MANE Select: NM_001350451
dbSNP: rs754135050
Type: single nucleotide variant
Location: chr17:79103234 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 62.27
Residue 145: the rrm domain

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.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
RBFOX3 p.Gln31Arg Uncertain significance ★★ ⚠ same condition
RBFOX3 p.Glu61Lys 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-phe145 (accessed [today's date]).

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