Is CCM2 p.Ter445Gly (c.1333T>G) pathogenic?

CCM2 p.Ter445Gly (c.1333T>G) is classified Uncertain significance in CCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-07). Very rare (popmax 6.85e-05%).

How common is CCM2 p.Ter445Gly (c.1333T>G) in the general population?

CCM2 p.Ter445Gly (c.1333T>G) is very rare (popmax 6.85e-05%) (gnomAD).

CCM2 p.Ter445Gly

c.1333T>G · rs1471483297 · VCV1810714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.3, phastCons 1
Overall
CADD	12.53	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,460,674 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CCM2
Protein: p.Ter445Gly
Coding: c.1333T>G
MANE Select: NM_031443
dbSNP: rs1471483297
Type: single nucleotide variant
Location: chr7:45076055 (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 c.289-1G>A Pathogenic/Likely pathogenic ★★ same type
CCM2 c.30+1G>A Pathogenic ★★ same type
CCM2 c.472+1G>C Pathogenic/Likely pathogenic ★★ same type
CCM2 c.473-1G>T Pathogenic ★★ same type
CCM2 c.745+1G>T Pathogenic ★★ same type
CCM2 p.Arg19Ter Pathogenic ★★ same type
CCM2 p.Arg57Ter Pathogenic/Likely pathogenic ★★ same type
CCM2 p.Gln107Ter 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-ter445gly (accessed [today's date]).

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