CCM2 p.Ser289=
c.867C>T · VCV3358228
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00271%, nfe)
Conditions
1
CCM2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.4 | GERP -3.5 |
| Overall | ||
| CADD | 3.009 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00271%
European (non-Finnish) · 32/1,179,922 alleles
Filtering AF
0.00196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00168%
Overall
0.00198%
32/1,612,954 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
- Protein
- p.Ser289=
- Coding
- c.867C>T
- MANE Select
- NM_031443
- Type
- single nucleotide variant
- Location
- chr7:45073523 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.48 · 8 PDB
- Residue 289
- a UniProt-annotated variant site (in); the 'harmonin homology domain' region; an α-helix
Disease context
CCM2-related disorder
Similar variants
- CCM2 p.Ser289Asn Benign ★★ ⚠ same residue
- CCM2 p.Gln107Ter Pathogenic ★★ same condition
- CCM2 p.Lys360Ter Pathogenic/Likely pathogenic ★★ same condition
- CCM2 c.205-2A>G Likely pathogenic ★ same condition
- CCM2 c.31-3C>A Uncertain significance ★ same condition
- CCM2 p.Met1Ile Conflicting classifications of pathogenicity ★ same condition
- CCM2 p.Glu54Ter Likely pathogenic same condition
- CCM2 p.Ala140Thr Uncertain significance ⚠ 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-ser289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown