Is CCM2 p.Val45fs (c.134_135del) pathogenic?

CCM2 p.Val45fs (c.134135del) is classified Pathogenic/Likely pathogenic in CCM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-02). Absent from gnomAD.

How common is CCM2 p.Val45fs (c.134_135del) in the general population?

CCM2 p.Val45fs (c.134_135del) is absent from gnomAD (gnomAD).

CCM2 p.Val45fs

c.134_135del · rs1562881980 · VCV590648

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7.4	GERP 0.36, 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.Val45fs
Coding: c.134_135del
MANE Select: NM_031443
dbSNP: rs1562881980
Type: Microsatellite
Location: chr7:45038354 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB

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

Similar variants

CCM2 p.Val45Leu Uncertain significance ★ ⚠ same residue
CCM2 p.Arg57fs Pathogenic ★★ same type
CCM2 p.Glu417fs Pathogenic/Likely pathogenic ★★ same type
CCM2 p.Ala171fs Pathogenic ★ same type
CCM2 p.Lys26_Ser27insTer Likely pathogenic ★ same type
CCM2 p.Thr44fs Pathogenic ★ same type

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-val45fs (accessed [today's date]).

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