Is CCM2 p.Arg19= (c.55C>A) pathogenic?

CCM2 p.Arg19= (c.55C>A) is classified Likely benign in CCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-04). Absent from gnomAD v4.1; Associated with cerebral cavernous malformation 2.

What condition is associated with CCM2 p.Arg19= (c.55C>A)?

CCM2 p.Arg19= (c.55C>A) is associated with cerebral cavernous malformation 2 (ClinVar).

How common is CCM2 p.Arg19= (c.55C>A) in the general population?

CCM2 p.Arg19= (c.55C>A) is absent from gnomAD v4.1 (gnomAD).

CCM2 p.Arg19=

c.55C>A · rs755800734 · VCV2021488

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.8	GERP 0.5, phastCons 1
Overall
CADD	11.74	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.Arg19=
Coding: c.55C>A
MANE Select: NM_031443
dbSNP: rs755800734
Type: single nucleotide variant
Location: chr7:45038277 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB
Residue 19: the 'disordered' region

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

CCM2 p.Arg19Ter 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.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-arg19 (accessed [today's date]).

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