Is CCM2 p.Lys203= (c.609G>A) pathogenic?

CCM2 p.Lys203= (c.609G>A) is classified Pathogenic/Likely pathogenic in CCM2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-11-22). Absent from gnomAD v4.1; Associated with cerebral cavernous malformation 2.

What condition is associated with CCM2 p.Lys203= (c.609G>A)?

CCM2 p.Lys203= (c.609G>A) is associated with cerebral cavernous malformation 2 (ClinVar).

How common is CCM2 p.Lys203= (c.609G>A) in the general population?

CCM2 p.Lys203= (c.609G>A) is absent from gnomAD v4.1 (gnomAD).

CCM2 p.Lys203=

c.609G>A · rs1562912528 · VCV590662

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cerebral cavernous malformation 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.019	moderately benign-leaning
Splicing
SpliceAI	Δ0.51	donor loss · deltas
Pangolin	Δ0.61	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.7	GERP 0.17, phastCons 1
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

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.Lys203=
Coding: c.609G>A
MANE Select: NM_031443
dbSNP: rs1562912528
Type: single nucleotide variant
Location: chr7:45068579 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB
Residue 203: the pid domain; an α-helix

Full CCM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebral cavernous malformation 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OSM p.His203Tyr Uncertain significance ★ ⚠ 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-lys203 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown