Is CCM2 p.Ile163fs (c.486del) pathogenic?

CCM2 p.Ile163fs (c.486del) is classified Likely pathogenic in CCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-28). Absent from gnomAD.

How common is CCM2 p.Ile163fs (c.486del) in the general population?

CCM2 p.Ile163fs (c.486del) is absent from gnomAD (gnomAD).

CCM2 p.Ile163fs

c.486del · rs2128749827 · VCV1212756

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.4	GERP -2.5

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.Ile163fs
Coding: c.486del
MANE Select: NM_031443
dbSNP: rs2128749827
Type: Deletion
Location: chr7:45068454 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB
Residue 163: the pid domain

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

Similar variants

CCM2 p.Ile163Val Uncertain significance ★★ ⚠ same residue
CCM2 p.Gln218fs Pathogenic ★★ same type
CCM2 p.Glu264fs Pathogenic/Likely pathogenic ★★ same type
CCM2 p.Gly24fs Pathogenic ★★ same type
CCM2 p.Lys26fs Pathogenic/Likely pathogenic ★★ same type
CCM2 p.Phe228fs Pathogenic/Likely pathogenic ★★ same type
CCM2 c.804-12del Benign/Likely benign ★★ same type
CCM2 c.289-19_352del Likely 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-ile163fs (accessed [today's date]).

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