RBFOX3 p.Pro86=
c.258G>A · rs1029382552 · VCV2079965
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0171%, mid)
Conditions
1
idiopathic generalized epilepsy
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 -4.1 | GERP -4.1 |
| Overall | ||
| CADD | 7.546 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0171%
Middle Eastern · 1/5,860 alleles
Filtering AF
0.00276%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00179%
Overall
0.00105%
16/1,524,094 alleles · ultra-rare
exomes 12/1,371,952 · genomes 4/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0171% | 5,860 |
| African / African-American | 0.00704% | 14,213 |
| East Asian | 0.00519% | 19,274 |
| South Asian | 0.00249% | 40,210 |
| Admixed American | 0.00218% | 45,836 |
| Finnishnot grpmax-eligible | 0.00172% | 58,202 |
| Remaining individualsnot grpmax-eligible | 0.0017% | 58,972 |
| European (non-Finnish) | 0.000264% | 378,834 |
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
- RBFOX3
- Protein
- p.Pro86=
- Coding
- c.258G>A
- MANE Select
- NM_001350451
- dbSNP
- rs1029382552
- Type
- single nucleotide variant
- Location
- chr17:79106753 (GRCh38)
- Gene constraint
- LOEUF 0.605 · pLI 0.60 (gnomAD)
- Structure
- AlphaFold pLDDT 62.27
- Residue 86
- the 'disordered' region
Similar variants
- RBFOX3 p.Pro86Leu Uncertain significance ★★ ⚠ same residue
- RBFOX3 p.Ala316Thr Uncertain significance ★★ ⚠ same condition
- RBFOX3 p.Ala62Val Uncertain significance ★★ ⚠ same condition
- RBFOX3 p.Ala68Thr Uncertain significance ★★ ⚠ same condition
- RBFOX3 p.Ala79Val Uncertain significance ★★ ⚠ same condition
- RBFOX3 p.Ala8Thr Uncertain significance ★★ ⚠ same condition
- RBFOX3 p.Arg230Trp Uncertain significance ★★ ⚠ same condition
- RBFOX3 p.Gln31Arg 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/rbfox3-p-pro86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown