CCM2 p.Ser183=
c.549G>A · rs145671290 · VCV1747911
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.047 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -8.2 | GERP -2.5 |
| Overall | ||
| CADD | 2.862 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,892 alleles
Filtering AF
0.00342%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0031%
Overall
0.00378%
61/1,614,038 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,964 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.00441% | 22,693 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| African / African-American | 0.00267% | 37,460 |
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.Ser183=
- Coding
- c.549G>A
- MANE Select
- NM_031443
- dbSNP
- rs145671290
- Type
- single nucleotide variant
- Location
- chr7:45068519 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.48 · 8 PDB
- Residue 183
- the pid domain
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-ser183 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown