Is CCM2 p.Tyr342= (c.1026C>T) pathogenic?

CCM2 p.Tyr342= (c.1026C>T) is classified Likely benign in CCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-08). Very rare (popmax 0.00223%, eas); Associated with cerebral cavernous malformation 2.

What condition is associated with CCM2 p.Tyr342= (c.1026C>T)?

CCM2 p.Tyr342= (c.1026C>T) is associated with cerebral cavernous malformation 2 (ClinVar).

How common is CCM2 p.Tyr342= (c.1026C>T) in the general population?

CCM2 p.Tyr342= (c.1026C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CCM2 p.Tyr342=

c.1026C>T · rs556953955 · VCV1634562

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

cerebral cavernous malformation 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -10	GERP -3.8
Overall
CADD	0.684	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00155% 25/1,613,384 alleles · very rare exomes 23/1,461,070 · genomes 2/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	0.00178%	56,187
Remaining individualsnot grpmax-eligible	0.0016%	62,496
Finnishnot grpmax-eligible	0.00158%	63,454
African / African-American	0.00133%	75,034

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.Tyr342=
Coding: c.1026C>T
MANE Select: NM_031443
dbSNP: rs556953955
Type: single nucleotide variant
Location: chr7:45074380 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB
Residue 342: the 'harmonin homology domain' region; an α-helix

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 c.289-1G>A Pathogenic/Likely pathogenic ★★ same condition
CCM2 c.30+1G>A Pathogenic ★★ same condition
CCM2 c.472+1G>C Pathogenic/Likely pathogenic ★★ same condition
CCM2 c.473-1G>T Pathogenic ★★ same condition
CCM2 c.745+1G>T Pathogenic ★★ same condition
CCM2 p.Arg19Ter Pathogenic ★★ same condition
CCM2 p.Arg57Ter Pathogenic/Likely pathogenic ★★ same condition
CCM2 p.Gln107Ter 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-tyr342 (accessed [today's date]).

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