CYFIP2 p.Pro738=
c.2214G>A · rs141399379 · VCV2413273
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00892%, eas)
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 -16 | GERP -3.6 |
| Overall | ||
| CADD | 0.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00892%
East Asian · 4/44,864 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.00136%
22/1,613,884 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00892% | 11,216 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| Admixed American | 0.00167% | 60,006 |
| European (non-Finnish) | 0.0011% | 90,758 |
| South Asian | 0.0011% | 91,080 |
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.Pro738=
- Coding
- c.2214G>A
- MANE Select
- NM_001037333
- dbSNP
- rs141399379
- Type
- single nucleotide variant
- Location
- chr5:157330799 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.28
Similar variants
- CYFIP2 p.Pro738Ser Uncertain significance ★★ ⚠ same residue
- CYFIP2 p.Pro738Arg Uncertain significance ★ ⚠ same residue
- CYFIP2 p.Pro738Leu Uncertain significance ★ ⚠ 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-pro738 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown