Is RBFOX2 p.Ala403Ser (c.1207G>T) pathogenic?

RBFOX2 p.Ala403Ser (c.1207G>T) is classified Uncertain significance in RBFOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). Very rare (popmax 0.00187%, nfe).

How common is RBFOX2 p.Ala403Ser (c.1207G>T) in the general population?

RBFOX2 p.Ala403Ser (c.1207G>T) is very rare (popmax 0.00187%, nfe) (gnomAD).

RBFOX2 p.Ala403Ser

c.1207G>T · rs1281377303 · VCV2954692

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.137	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.5, phastCons 1
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00187% European (non-Finnish) · 22/1,174,760 alleles

Filtering AF 0.00123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00143% 23/1,604,516 alleles · very rare exomes 23/1,452,418 · genomes 0/152,098 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00187%	53,398
Remaining individualsnot grpmax-eligible	0.00161%	62,068

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.Ala403Ser
Coding: c.1207G>T
MANE Select: NM_001349999
dbSNP: rs1281377303
Type: single nucleotide variant
Location: chr22:35746492 (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

Similar variants

RBFOX2 p.Ala403Val Uncertain significance ★ same residue
RBFOX2 p.Ala403_Ala405del Benign ★ same residue
RBFOX2 p.Asp417Asn Uncertain significance ★★ same type
RBFOX2 p.Asp41His Uncertain significance ★★ same type
RBFOX2 p.Glu229Gln Uncertain significance ★★ same type
RBFOX2 p.Gly133Arg Uncertain significance ★★ same type
RBFOX2 p.Gly409Ser Uncertain significance ★★ same type
RBFOX2 p.Met91Val Uncertain significance ★★ same type

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-ala403ser (accessed [today's date]).

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