CCN6 p.Pro307=
c.921T>C · rs369476308 · VCV2752914
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
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 -0.044 | GERP -3.9, phastCons 0.88 |
| Overall | ||
| CADD | 6.553 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,994 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.00155%
25/1,613,788 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 9,999 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,831 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,588 |
| European (non-Finnish) | 0.00127% | 78,656 |
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
- CCN6
- Protein
- p.Pro307=
- Coding
- c.921T>C
- MANE Select
- NM_198239
- dbSNP
- rs369476308
- Type
- single nucleotide variant
- Location
- chr6:112069476 (GRCh38)
- Gene constraint
- LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.30
- Residue 307
- a disulfide bond; a UniProt-annotated variant site (in pprd); the ctck domain
Similar variants
- CCN6 c.49-1G>A Pathogenic/Likely pathogenic ★★ same type
- CCN6 c.590-1G>C Likely pathogenic ★★ same type
- CCN6 p.Ala197Pro Pathogenic/Likely pathogenic ★★ ⚠ same type
- CCN6 p.Cys223Gly Pathogenic ★★ same type
- CCN6 p.Cys337Tyr Pathogenic/Likely pathogenic ★★ same type
- CCN6 p.Cys52Ter Pathogenic/Likely pathogenic ★★ same type
- CCN6 p.Cys78Tyr Pathogenic/Likely pathogenic ★★ same type
- CCN6 p.Met1Val Pathogenic/Likely 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/ccn6-p-pro307 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown