CCN6 p.Cys252=
c.756C>T · rs375253675 · VCV2882306
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, afr)
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 -1 | GERP -5.4 |
| Overall | ||
| CADD | 2.829 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/74,928 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00459%
74/1,612,404 alleles · ultra-rare
exomes 61/1,460,330 · genomes 13/152,074 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,568 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,900 |
| South Asian | 0.00881% | 11,354 |
| East Asian | 0.0067% | 14,925 |
| Admixed American | 0.00501% | 19,947 |
| European (non-Finnish) | 0.00195% | 51,269 |
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.Cys252=
- Coding
- c.756C>T
- MANE Select
- NM_198239
- dbSNP
- rs375253675
- Type
- single nucleotide variant
- Location
- chr6:112068371 (GRCh38)
- Gene constraint
- LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.30
- Residue 252
- a UniProt-annotated variant site (in pprd); the tsp type-1 domain
Similar variants
- CCN6 p.Cys252Ter Pathogenic ★ same residue
- 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
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-cys252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown