Is RBFOX2 p.Ala18= (c.54C>G) pathogenic?

RBFOX2 p.Ala18= (c.54C>G) is classified Likely benign in RBFOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). Very rare (popmax 0.00309%, eas).

How common is RBFOX2 p.Ala18= (c.54C>G) in the general population?

RBFOX2 p.Ala18= (c.54C>G) is very rare (popmax 0.00309%, eas) (gnomAD).

RBFOX2 p.Ala18=

c.54C>G · rs985653339 · VCV1670791

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00309%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.94	GERP -2, phastCons 1
Overall
CADD	9.512	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00309% East Asian · 1/32,354 alleles

Overall 0.000146% 2/1,370,312 alleles · very rare exomes 2/1,218,540 · genomes 0/151,772 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00309%	32,354
Remaining individualsnot grpmax-eligible	0.00195%	51,210

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.Ala18=
Coding: c.54C>G
MANE Select: NM_001349999
dbSNP: rs985653339
Type: single nucleotide variant
Location: chr22:36028372 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 1 PDB
Residue 18: the 'disordered' region

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

Similar variants

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
RBFOX2 p.Pro104Leu Uncertain significance ★★ same type
RBFOX2 p.Pro307Ser 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-ala18 (accessed [today's date]).

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