Is RBFOX2 p.Ala401= (c.1203C>T) pathogenic?

RBFOX2 p.Ala401= (c.1203C>T) is classified Likely benign in RBFOX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-09). Ultra-rare (popmax 0.0255%, afr); Associated with Inborn genetic diseases.

What condition is associated with RBFOX2 p.Ala401= (c.1203C>T)?

RBFOX2 p.Ala401= (c.1203C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RBFOX2 p.Ala401= (c.1203C>T) in the general population?

RBFOX2 p.Ala401= (c.1203C>T) is ultra-rare (popmax 0.0255%, afr) (gnomAD).

RBFOX2 p.Ala401=

c.1203C>T · VCV3711839

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0255%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.064	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -2, phastCons 0.74
Overall
CADD	13.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0255% African / African-American · 19/74,548 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00249% 40/1,606,406 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0255%	3,924
Admixed American	0.0169%	5,904
Remaining individualsnot grpmax-eligible	0.00161%	62,120
Finnishnot grpmax-eligible	0.00157%	63,882
South Asian	0.00111%	90,426
European (non-Finnish)	0.000681%	146,941

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: RBFOX2
Protein: p.Ala401=
Coding: c.1203C>T
MANE Select: NM_001349999
Type: single nucleotide variant
Location: chr22:35746496 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 1 PDB

Full RBFOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBFOX2 p.Asp417Asn Uncertain significance ★★ same condition
RBFOX2 p.Glu229Gln Uncertain significance ★★ same condition
RBFOX2 p.Gly133Arg Uncertain significance ★★ same condition
RBFOX2 p.Gly409Ser Uncertain significance ★★ same condition
RBFOX2 p.Met91Val Uncertain significance ★★ same condition
RBFOX2 p.Pro104Leu Uncertain significance ★★ same condition
RBFOX2 p.Pro307Ser Uncertain significance ★★ same condition
RBFOX2 p.Tyr406Ter Pathogenic ★ 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/rbfox2-p-ala401 (accessed [today's date]).

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