CCN1 p.Ala366=
c.1098G>A · VCV3997534
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 -9.9 | GERP -3.2 |
| Overall | ||
| CADD | 1.097 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,072 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000274%
4/1,461,736 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,536 |
| European (non-Finnish) | 0.00017% | 589,957 |
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
- CCN1
- Protein
- p.Ala366=
- Coding
- c.1098G>A
- MANE Select
- NM_001237 · reported on NM_001554
- Type
- single nucleotide variant
- Location
- chr1:85582994 (GRCh38)
- Structure
- AlphaFold pLDDT 73.80 · 115 PDB
- Residue 366
- an α-helix
Similar variants
- EXOSC9 p.Ala438Val Uncertain significance ★★ ⚠ same type
- CCN1 c.277+50G>C Benign ★★ same type
- CCN1 c.64-124G>A Benign ★★ same type
- CCN1 c.-107C>A Benign ★★ same type
- CCN1 p.Ser316Cys Likely benign ★★ ⚠ same type
- CCN1 p.Tyr300= Benign ★★ same type
- CCNA2 c.*828C>G Benign ★★ same type
- CCNA2 p.Leu126= Benign ★★ 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/ccn1-p-ala366 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown