CCM2 p.His323=
c.969C>T · rs546816313 · VCV2451701
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0154%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -3.8 |
| Overall | ||
| CADD | 1.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0154%
South Asian · 14/91,090 alleles
Filtering AF
0.00919%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00735%
Overall
0.00273%
44/1,613,786 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0154% | 6,506 |
| East Asian | 0.00446% | 22,443 |
| Admixed American | 0.00333% | 30,011 |
| European (non-Finnish) | 0.00203% | 49,168 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| African / African-American | 0.00133% | 75,072 |
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.His323=
- Coding
- c.969C>T
- MANE Select
- NM_031443
- dbSNP
- rs546816313
- Type
- single nucleotide variant
- Location
- chr7:45074323 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.48 · 8 PDB
- Residue 323
- the 'harmonin homology domain' region; an α-helix
Similar variants
- CCM2 p.Ala186Thr Uncertain significance ★★ ⚠ same condition
- CCM2 p.Arg326His Uncertain significance ★★ ⚠ same condition
- CCM2 p.Arg423Pro Uncertain significance ★★ ⚠ same condition
- CCM2 p.Gln441Arg Uncertain significance ★★ ⚠ same condition
- CCM2 p.Ile131Asn Uncertain significance ★★ ⚠ same condition
- CCM2 p.Pro102Leu Uncertain significance ★★ ⚠ same condition
- CCM2 p.Val374Met Uncertain significance ★★ ⚠ same condition
- CCM2 p.Arg378= Likely benign ★★ 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-his323 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown