Is RBFOX1 p.Pro24Ser (c.70C>T) pathogenic?

RBFOX1 p.Pro24Ser (c.70C>T) is classified Benign in RBFOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-14). AlphaMissense: likely benign (0.1135); Ultra-rare (popmax 0.015%, amr); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX1 p.Pro24Ser (c.70C>T)?

RBFOX1 p.Pro24Ser (c.70C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX1 p.Pro24Ser (c.70C>T) in the general population?

RBFOX1 p.Pro24Ser (c.70C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about RBFOX1 p.Pro24Ser (c.70C>T)?

AlphaMissense predicts likely benign (score 0.1135) — an in-silico prediction, not a clinical call.

RBFOX1 p.Pro24Ser

c.70C>T · rs148751394 · VCV1166055

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1135 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
AlphaMissense	0.1135	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -9.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.54	unconstrained · MANE · 528 kb · p 9.7e-12 · regional, not allelic
Overall
CADD	25.8	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 0.015% Admixed American · 9/59,994 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.0171% 276/1,613,854 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.642%	156
Remaining individualsnot grpmax-eligible	0.0496%	2,016
Admixed Americangrpmax	0.015%	6,666
European (non-Finnish)	0.00381%	26,220
South Asian	0.0011%	91,054

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro24Ser
Coding: c.70C>T
MANE Select: NM_018723
dbSNP: rs148751394
Type: single nucleotide variant
Location: chr16:7518189 (GRCh38)
Gene constraint: LOEUF 0.311 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.23 · 4 PDB
Residue 24: 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.Leu24Val Uncertain significance ★ same residue
RBFOX1 p.Pro24= Likely benign ★ 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-pro24ser (accessed [today's date]).

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