CCM2 p.Lys375=
c.1125G>A · rs1583998841 · VCV741515
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 5 | GERP -3.5, phastCons 1 |
| Overall | ||
| CADD | 8.044 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,046 alleles
Overall
6.84e-05%
1/1,461,404 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.Lys375=
- Coding
- c.1125G>A
- MANE Select
- NM_031443
- dbSNP
- rs1583998841
- Type
- single nucleotide variant
- Location
- chr7:45075847 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.48 · 8 PDB
- Residue 375
- the 'harmonin homology domain' region; a turn
Similar variants
- CCM2 p.Lys375Glu Uncertain significance ★ ⚠ 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
- CCM2 p.Arg57Ter Pathogenic/Likely 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-lys375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown