CYFIP2 p.Glu433=
c.1299A>G · rs372259482 · VCV1571215
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.456%, sas)
Conditions
1
developmental and epileptic encephalopathy, 65
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP 0.22, phastCons 1 |
| Overall | ||
| CADD | 4.673 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.456%
South Asian · 412/90,432 alleles
Filtering AF
0.419%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.405%
Overall
0.0291%
469/1,612,296 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.456% | 219 |
| Middle Eastern | 0.099% | 1,010 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,313 |
| East Asian | 0.0401% | 2,493 |
| Admixed American | 0.00167% | 59,782 |
| European (non-Finnish) | 0.000424% | 235,855 |
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
- CYFIP2
- Protein
- p.Glu433=
- Coding
- c.1299A>G
- MANE Select
- NM_001037333
- dbSNP
- rs372259482
- Type
- single nucleotide variant
- Location
- chr5:157315037 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.28
Similar variants
- CYFIP2 p.Arg87Cys Pathogenic/Likely pathogenic ★★ same condition
- CYFIP2 p.Arg87Pro Pathogenic/Likely pathogenic ★★ same condition
- CYFIP2 p.Glu640Lys Pathogenic ★★ same condition
- CYFIP2 p.Tyr108His Likely pathogenic ★★ ⚠ same condition
- CYFIP2 p.Arg1045Trp Uncertain significance ★★ ⚠ same condition
- CYFIP2 p.Arg353Trp Uncertain significance ★★ ⚠ same condition
- CYFIP2 p.Asp821Asn Uncertain significance ★★ ⚠ same condition
- CYFIP2 p.His417Asn 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/cyfip2-p-glu433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown