Is CCM2 p.Arg28fs (c.83_87del) pathogenic?

CCM2 p.Arg28fs (c.8387del) is classified Pathogenic in CCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). Absent from gnomAD; Associated with cerebral cavernous malformation 2.

What condition is associated with CCM2 p.Arg28fs (c.83_87del)?

CCM2 p.Arg28fs (c.83_87del) is associated with cerebral cavernous malformation 2 (ClinVar).

How common is CCM2 p.Arg28fs (c.83_87del) in the general population?

CCM2 p.Arg28fs (c.83_87del) is absent from gnomAD (gnomAD).

CCM2 p.Arg28fs

c.83_87del · rs2128729105 · VCV1458144

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cerebral cavernous malformation 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP -3.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCM2
Protein: p.Arg28fs
Coding: c.83_87del
MANE Select: NM_031443
dbSNP: rs2128729105
Type: Deletion
Location: chr7:45038305 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB
Residue 28: 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.Gln218fs Pathogenic ★★ same condition
CCM2 p.Glu264fs Pathogenic/Likely pathogenic ★★ same condition
CCM2 p.Gly24fs Pathogenic ★★ same condition
CCM2 p.Phe228fs Pathogenic/Likely pathogenic ★★ same condition
CCM2 c.804-12del Benign/Likely benign ★★ same condition
CCM2 p.Ala32fs Pathogenic ★ same condition
CCM2 p.Asn119fs Likely pathogenic ★ same condition
CCM2 p.Asp56fs 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-arg28fs (accessed [today's date]).

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