CCM2 p.Ser173Arg
c.517A>C · VCV4529936
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5278 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5278 | ambiguous |
|---|---|---|
| REVEL | 0.061 | moderately benign-leaning |
| SaProt | LLR -6.76 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP -0.83, phastCons 1 |
| Regional constraint | o/e 0.83 | unconstrained · MANE · 76 kb · p 3.5e-05 · regional, not allelic |
| Overall | ||
| CADD | 18.85 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CCM2
- Protein
- p.Ser173Arg
- Coding
- c.517A>C
- MANE Select
- NM_031443
- Type
- single nucleotide variant
- Location
- chr7:45068487 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.48 · 8 PDB
- Residue 173
- the pid domain
Similar variants
- 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
- CCM2 p.Gln107Ter 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-ser173arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown