RBFOX2 p.Ala335=
c.1005C>T · VCV3632403
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.12%, afr)
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 -0.087 | GERP -5.4, phastCons 0.12 |
| Overall | ||
| CADD | 7.801 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.12%
African / African-American · 90/75,008 alleles
Filtering AF
0.0999%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0925%
Overall
0.00799%
129/1,613,864 alleles · rare
exomes 71/1,461,594 · genomes 58/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.12% | 833 |
| South Asian | 0.0198% | 5,059 |
| Admixed American | 0.01% | 10,004 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,497 |
| East Asian | 0.00668% | 14,960 |
| European (non-Finnish) | 0.000593% | 168,577 |
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.Ala335=
- Coding
- c.1005C>T
- MANE Select
- NM_001349999
- Type
- single nucleotide variant
- Location
- chr22:35759980 (GRCh38)
- Gene constraint
- LOEUF 0.336 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 55.86 · 1 PDB
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-ala335 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown