CYFIP2 p.Ser180=
c.540C>T · rs373151265 · VCV1615503
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0332%, mid)
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 -8.9 | GERP -3.6 |
| Overall | ||
| CADD | 5.646 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0332%
Middle Eastern · 2/6,026 alleles
Filtering AF
0.0201%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0193%
Overall
0.0175%
281/1,604,420 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0332% | 3,013 |
| European (non-Finnish) | 0.0224% | 4,464 |
| East Asian | 0.0112% | 8,906 |
| Remaining individualsnot grpmax-eligible | 0.00484% | 20,647 |
| South Asian | 0.00444% | 22,536 |
| African / African-American | 0.00402% | 24,898 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00344% | 29,088 |
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.Ser180=
- Coding
- c.540C>T
- MANE Select
- NM_001037333
- dbSNP
- rs373151265
- Type
- single nucleotide variant
- Location
- chr5:157300867 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.28
Similar variants
- FNDC9 p.Leu180Gln 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
- CYFIP2 p.Ala773Thr Uncertain significance ★★ ⚠ same type
- CYFIP2 p.Ala80Val 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-ser180 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown