CCN6 p.Cys268=
c.804C>T · rs199512487 · VCV2656858
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0494%, mid)
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 0.001 | GERP 0.11, phastCons 0.82 |
| Overall | ||
| CADD | 5.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0494%
Middle Eastern · 3/6,076 alleles
Filtering AF
0.0141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0112%
Overall
0.0044%
71/1,613,210 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0494% | 2,025 |
| Admixed American | 0.0234% | 4,282 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,409 |
| South Asian | 0.00439% | 22,763 |
| European (non-Finnish) | 0.00373% | 26,814 |
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.Cys268=
- Coding
- c.804C>T
- MANE Select
- NM_198239
- dbSNP
- rs199512487
- Type
- single nucleotide variant
- Location
- chr6:112069359 (GRCh38)
- Gene constraint
- LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.30
- Residue 268
- a disulfide bond; a UniProt-annotated variant site (in pprd); a UniProt-annotated variant site (in pprd; uncertain significance); 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-cys268 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown