CCN4 p.Cys273=
c.819T>C · VCV3487325
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0214%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.1 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.68 | GERP -3.8 |
| Overall | ||
| CADD | 5.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0214%
African / African-American · 16/74,876 alleles
Filtering AF
0.0133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0109%
Overall
0.0013%
21/1,612,112 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0214% | 4,680 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,374 |
| European (non-Finnish) | 0.000339% | 294,703 |
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
- CCN4
- Protein
- p.Cys273=
- Coding
- c.819T>C
- MANE Select
- NM_003882
- Type
- single nucleotide variant
- Location
- chr8:133227425 (GRCh38)
- Gene constraint
- LOEUF 1.151 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.16
- Residue 273
- a disulfide bond; the ctck domain
Similar variants
- CCN4 p.Arg97= Benign ★★ same type
- CCN4 p.Leu99= Benign ★★ same type
- CCN4 p.Thr145Met Likely benign ★★ ⚠ same type
- CCN4 p.Ala10Glu Uncertain significance ★ ⚠ same type
- CCN4 p.Ala10Thr Uncertain significance ★ ⚠ same type
- CCN4 p.Ala17Ser Uncertain significance ★ ⚠ same type
- CCN4 p.Ala196Thr Uncertain significance ★ ⚠ same type
- CCN4 p.Ala243Ser Uncertain significance ★ ⚠ 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/ccn4-p-cys273 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown