Is CCM2 p.Val204= (c.612C>T) pathogenic?

CCM2 p.Val204= (c.612C>T) is classified Likely benign in CCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-21). Ultra-rare (popmax 0.0446%, eas); Associated with cerebral cavernous malformation 2.

What condition is associated with CCM2 p.Val204= (c.612C>T)?

CCM2 p.Val204= (c.612C>T) is associated with cerebral cavernous malformation 2 (ClinVar).

How common is CCM2 p.Val204= (c.612C>T) in the general population?

CCM2 p.Val204= (c.612C>T) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

CCM2 p.Val204=

c.612C>T · rs181474100 · VCV468337

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Conditions

cerebral cavernous malformation 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.003	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.6	GERP -3
Overall
CADD	0.389	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0446% East Asian · 20/44,888 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00353% 57/1,614,098 alleles · ultra-rare exomes 48/1,461,728 · genomes 9/152,370 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,244
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00333%	30,014
African / African-American	0.00266%	37,538
European (non-Finnish)	0.00212%	47,202

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.Val204=
Coding: c.612C>T
MANE Select: NM_031443
dbSNP: rs181474100
Type: single nucleotide variant
Location: chr7:45069828 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB
Residue 204: the pid domain; 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-val204 (accessed [today's date]).

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