CCM2 c.288+3A>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.54e-05%, nfe)
Conditions
1
cerebral cavernous malformation 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +3 | donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.94 | donor loss · deltas |
| Pangolin | Δ0.76 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.4 | GERP 0.53, phastCons 1 |
| Non-coding constraint | Z 2.29 | 1 kb window · o/e 0.85 · regional · uncalibrated |
| Overall | ||
| CADD | 14.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.54e-05%
European (non-Finnish) · 1/1,170,500 alleles
Overall
0.000658%
1/152,078 alleles · very rare
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
- Coding
- c.288+3A>C
- MANE Select
- NM_031443
- Type
- single nucleotide variant
- Location
- chr7:45064004 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.48 · 8 PDB
Similar variants
- CCM2 c.289-1G>A Pathogenic/Likely pathogenic ★★ same condition
- CCM2 c.30+1G>A Pathogenic ★★ same condition
- CCM2 c.472+1G>C Pathogenic/Likely pathogenic ★★ same condition
- CCM2 c.473-1G>T Pathogenic ★★ same condition
- CCM2 c.745+1G>T Pathogenic ★★ same condition
- CCM2 p.Arg19Ter Pathogenic ★★ same condition
- CCM2 p.Arg57Ter Pathogenic/Likely pathogenic ★★ same condition
- CCM2 p.Gln107Ter 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-c-288-plus-3a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown