CCM2 p.Ile226=
c.678C>T · VCV4683266
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00254%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.076 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.94 | GERP -1.6, phastCons 0.002 |
| Overall | ||
| CADD | 11.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00254%
European (non-Finnish) · 30/1,180,026 alleles
Filtering AF
0.0018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00156%
Overall
0.00192%
31/1,614,040 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00254% | 39,334 |
| East Asian | 0.00223% | 44,890 |
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
- CCM2
- Protein
- p.Ile226=
- Coding
- c.678C>T
- MANE Select
- NM_031443
- Type
- single nucleotide variant
- Location
- chr7:45069894 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.48 · 8 PDB
- Residue 226
- the pid domain; an α-helix
Similar variants
- CCM2 p.Ile226Ser Uncertain significance ★ ⚠ same residue
- CCM2 p.Ile226Val Likely benign ★ same residue
- CCM2 c.289-1G>A Pathogenic/Likely pathogenic ★★ same type
- CCM2 c.30+1G>A Pathogenic ★★ same type
- CCM2 c.472+1G>C Pathogenic/Likely pathogenic ★★ same type
- CCM2 c.473-1G>T Pathogenic ★★ same type
- CCM2 c.745+1G>T Pathogenic ★★ same type
- CCM2 p.Arg19Ter Pathogenic ★★ 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/ccm2-p-ile226 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown