Is RBFOX1 p.Pro48Ser (c.142C>T) pathogenic?

RBFOX1 p.Pro48Ser (c.142C>T) is classified Likely benign in RBFOX1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.0878); Rare (popmax 0.107%, nfe); Associated with idiopathic generalized epilepsy.

What condition is associated with RBFOX1 p.Pro48Ser (c.142C>T)?

RBFOX1 p.Pro48Ser (c.142C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is RBFOX1 p.Pro48Ser (c.142C>T) in the general population?

RBFOX1 p.Pro48Ser (c.142C>T) is rare (popmax 0.107%, nfe) (gnomAD).

What do computational predictors say about RBFOX1 p.Pro48Ser (c.142C>T)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

RBFOX1 p.Pro48Ser

c.142C>T · rs151214012 · VCV410097

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.107%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -8.46	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 1.7, phastCons 1
Regional constraint	o/e 1.54	unconstrained · MANE · 528 kb · p 9.7e-12 · regional, not allelic
Overall
CADD	26.8	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 0.107% European (non-Finnish) · 1,257/1,180,034 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0996%

Overall 0.0913% 1,473/1,614,040 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.226%	442
European (non-Finnish)grpmax	0.107%	939
Finnishnot grpmax-eligible	0.0859%	1,164
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Admixed American	0.0417%	2,400
African / African-American	0.0227%	4,407

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.Pro48Ser
Coding: c.142C>T
MANE Select: NM_018723
dbSNP: rs151214012
Type: single nucleotide variant
Location: chr16:7518261 (GRCh38)
Gene constraint: LOEUF 0.311 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.23 · 4 PDB
Residue 48: 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.Pro48= 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
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-pro48ser (accessed [today's date]).

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