CCM2 p.Glu259=
c.777G>A · rs765305537 · VCV765597
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, eas)
Conditions
1
cerebral cavernous malformation 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.038 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.92 | GERP -3.5, phastCons 0.22 |
| Overall | ||
| CADD | 7.718 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
East Asian · 12/44,890 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.000822%
12/1,460,556 alleles · ultra-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
- Protein
- p.Glu259=
- Coding
- c.777G>A
- MANE Select
- NM_031443
- dbSNP
- rs765305537
- Type
- single nucleotide variant
- Location
- chr7:45072757 (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-p-glu259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown