CYFIP2 p.Pro117=
c.351G>A · rs566420283 · VCV2428421
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, amr)
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 -12 | GERP -3.3 |
| Overall | ||
| CADD | 0.304 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
Admixed American · 9/60,018 alleles
Filtering AF
0.00773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00578%
Overall
0.00248%
40/1,613,770 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.015% | 6,669 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,232 |
| European (non-Finnish) | 0.0022% | 45,374 |
| South Asian | 0.0022% | 45,533 |
| African / African-American | 0.00133% | 75,050 |
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.Pro117=
- Coding
- c.351G>A
- MANE Select
- NM_001037333
- dbSNP
- rs566420283
- Type
- single nucleotide variant
- Location
- chr5:157296738 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.28
Similar variants
- CYFIP2 p.Pro117Gln Uncertain significance ★ ⚠ same residue
- CYFIP2 p.Pro117Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- CYFIP2 p.Pro117Leu Likely benign ★ same residue
- CYFIP2 p.Arg87Cys Pathogenic/Likely pathogenic ★★ same type
- CYFIP2 p.Arg87Pro Pathogenic/Likely pathogenic ★★ same type
- CYFIP2 p.Glu640Lys Pathogenic ★★ same type
- CYFIP2 p.Tyr108His Likely pathogenic ★★ ⚠ same type
- CYFIP2 p.Ala1074Thr 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/cyfip2-p-pro117 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown