Is CCM2 p.Ser143del (c.428_430del) pathogenic?

CCM2 p.Ser143del (c.428430del) is classified Uncertain significance in CCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-24). Absent from gnomAD; Associated with cerebral cavernous malformation 2.

What condition is associated with CCM2 p.Ser143del (c.428_430del)?

CCM2 p.Ser143del (c.428_430del) is associated with cerebral cavernous malformation 2 (ClinVar).

How common is CCM2 p.Ser143del (c.428_430del) in the general population?

CCM2 p.Ser143del (c.428_430del) is absent from gnomAD (gnomAD).

CCM2 p.Ser143del

c.428_430del · rs1562907973 · VCV575300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 0.69, phastCons 1

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.Ser143del
Coding: c.428_430del
MANE Select: NM_031443
dbSNP: rs1562907973
Type: Deletion
Location: chr7:45064600 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB
Residue 143: the pid domain; a β-strand

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.Ser143Pro Uncertain significance ★ ⚠ same residue
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.Arg28fs 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-ser143del (accessed [today's date]).

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