Is RBFOX2 p.Ala403Val (c.1208C>T) pathogenic?

RBFOX2 p.Ala403Val (c.1208C>T) is classified Uncertain significance in RBFOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-05). Very rare (popmax 6.23e-05%); Associated with Inborn genetic diseases.

What condition is associated with RBFOX2 p.Ala403Val (c.1208C>T)?

RBFOX2 p.Ala403Val (c.1208C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RBFOX2 p.Ala403Val (c.1208C>T) in the general population?

RBFOX2 p.Ala403Val (c.1208C>T) is very rare (popmax 6.23e-05%) (gnomAD).

RBFOX2 p.Ala403Val

c.1208C>T · VCV3313135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.23e-05%)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.207	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.23e-05%

Overall 6.23e-05% 1/1,604,270 alleles · very rare exomes 1/1,452,190 · genomes 0/152,080 · joint denominator

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.Ala403Val
Coding: c.1208C>T
MANE Select: NM_001349999
Type: single nucleotide variant
Location: chr22:35746491 (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.Ala403Ser Uncertain significance ★ same residue
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

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-ala403val (accessed [today's date]).

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