CCM2 p.Glu54Lys
c.160G>A · rs759104121 · VCV1054801
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5152 | ambiguous |
|---|---|---|
| REVEL | 0.199 | benign-leaning |
| SaProt | LLR -8.15 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.32 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.83 | unconstrained · MANE · 76 kb · p 3.5e-05 · regional, not allelic |
| Overall | ||
| CADD | 29.8 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| Admixed Americangrpmax | 0.005% | 20,008 |
| European (non-Finnish) | 0.00483% | 20,702 |
| African / African-American | 0.00133% | 75,024 |
| South Asian | 0.0011% | 91,082 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Glu54Lys
- Coding
- c.160G>A
- MANE Select
- NM_031443
- dbSNP
- rs759104121
- Type
- single nucleotide variant
- Location
- chr7:45038382 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.48 · 8 PDB
Similar variants
- CCM2 p.Glu54Ter Likely pathogenic same residue
- 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
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-glu54lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown