Is RBFOX1 p.Ser86Phe (c.257C>T) pathogenic?

RBFOX1 p.Ser86Phe (c.257C>T) is classified Uncertain significance in RBFOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: ambiguous (0.351); Very rare (popmax 8.5e-05%, nfe); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX1 p.Ser86Phe (c.257C>T)?

RBFOX1 p.Ser86Phe (c.257C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX1 p.Ser86Phe (c.257C>T) in the general population?

RBFOX1 p.Ser86Phe (c.257C>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about RBFOX1 p.Ser86Phe (c.257C>T)?

AlphaMissense predicts ambiguous (score 0.351) — an in-silico prediction, not a clinical call.

RBFOX1 p.Ser86Phe

c.257C>T · rs2152190628 · VCV2892700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.351 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
AlphaMissense	0.351	ambiguous
REVEL	0.2	benign-leaning
SaProt	LLR -12.06	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.54	unconstrained · MANE · 528 kb · p 9.7e-12 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,498 alleles

Overall 6.86e-05% 1/1,456,764 alleles · very rare

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.Ser86Phe
Coding: c.257C>T
MANE Select: NM_018723
dbSNP: rs2152190628
Type: single nucleotide variant
Location: chr16:7518376 (GRCh38)
Gene constraint: LOEUF 0.311 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.23 · 4 PDB
Residue 86: 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.Ser86Cys 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-ser86phe (accessed [today's date]).

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