CDC42BPB p.Ser659=
c.1977C>T · VCV4873070
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.154%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.48 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.31 | gain · loss 0.04 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -1 | GERP -4.2 |
| Overall | ||
| CADD | 16.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.154%
East Asian · 69/44,876 alleles
Filtering AF
0.125%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.114%
Overall
0.00502%
81/1,613,288 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.154% | 650 |
| South Asian | 0.0055% | 18,181 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,815 |
| African / African-American | 0.004% | 25,015 |
| Finnishnot grpmax-eligible | 0.00156% | 63,980 |
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
- CDC42BPB
- Protein
- p.Ser659=
- Coding
- c.1977C>T
- MANE Select
- NM_006035
- Type
- single nucleotide variant
- Location
- chr14:102970169 (GRCh38)
- Gene constraint
- LOEUF 0.235 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.28 · 6 PDB
Similar variants
- CDC42BPB c.2726+1G>A Pathogenic/Likely pathogenic ★★ same type
- CDC42BPB p.Ala177Val Likely pathogenic ★★ same type
- CDC42BPB p.Arg122Ter Pathogenic/Likely pathogenic ★★ same type
- CDC42BPB p.Arg867Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- CDC42BPB p.Arg876Pro Likely pathogenic ★★ ⚠ same type
- CDC42BPB p.Asp175Tyr Likely pathogenic ★★ same type
- CDC42BPB p.Ser1530Ter Likely pathogenic ★★ same type
- CDC42BPB p.Arg509Ter 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/cdc42bpb-p-ser659 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown