CCM2 p.Ile136fs
c.405del · VCV4895971
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
CCM2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 10 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.75 | GERP 0.67, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CCM2
- Protein
- p.Ile136fs
- Coding
- c.405del
- MANE Select
- NM_031443
- Type
- Deletion
- Location
- chr7:45064577 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.48 · 8 PDB
- Residue 136
- the pid domain; an α-helix
Disease context
CCM2-related disorder
Similar variants
- CCM2 p.Lys26fs Pathogenic/Likely pathogenic ★★ same condition
- CCM2 p.Ala150fs Likely pathogenic ★ same condition
- CCM2 p.Asp230fs Likely pathogenic ★ same condition
- CCM2 p.Leu47fs Likely pathogenic ★ same condition
- CCM2 p.Lys30fs Likely pathogenic ★ same condition
- CCM2 p.Gln107Ter Pathogenic ★★ same condition
- CCM2 p.Lys360Ter Pathogenic/Likely pathogenic ★★ same condition
- CCM2 c.205-2A>G Likely pathogenic ★ 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/ccm2-p-ile136fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown