Is RBFOX2 p.Val413Met (c.1237G>A) pathogenic?

RBFOX2 p.Val413Met (c.1237G>A) is classified Uncertain significance in RBFOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with RBFOX2 p.Val413Met (c.1237G>A)?

RBFOX2 p.Val413Met (c.1237G>A) is associated with Inborn genetic diseases (ClinVar).

How common is RBFOX2 p.Val413Met (c.1237G>A) in the general population?

RBFOX2 p.Val413Met (c.1237G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

RBFOX2 p.Val413Met

c.1237G>A · VCV3431066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.259	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,026 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,613,462 alleles · very rare exomes 2/1,461,264 · genomes 0/152,198 · 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.Val413Met
Coding: c.1237G>A
MANE Select: NM_001349999
Type: single nucleotide variant
Location: chr22:35745985 (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.Val413Leu 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-val413met (accessed [today's date]).

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