CCN5 p.Pro84=
c.252C>T · rs376446751 · VCV3139831
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0532%, 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 -2.3 | GERP -3.2 |
| Overall | ||
| CADD | 1.874 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0532%
South Asian · 46/86,446 alleles
Filtering AF
0.041%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0366%
Overall
0.018%
281/1,562,400 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0532% | 1,879 |
| European (non-Finnish) | 0.0195% | 5,134 |
| Remaining individualsnot grpmax-eligible | 0.00821% | 12,184 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00348% | 28,726 |
| East Asian | 0.00232% | 43,090 |
| Admixed American | 0.00188% | 53,264 |
| African / African-American | 0.00135% | 74,314 |
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
- CCN5
- Protein
- p.Pro84=
- Coding
- c.252C>T
- MANE Select
- NM_003881
- dbSNP
- rs376446751
- Type
- single nucleotide variant
- Location
- chr20:44720088 (GRCh38)
- Gene constraint
- LOEUF 1.47 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.59
- Residue 84
- a disulfide bond; the igfbp n-terminal domain
Similar variants
- CCN5 p.Leu169= Benign ★★ same type
- CCN5 p.Ala11Asp Uncertain significance ★ same type
- CCN5 p.Ala213Thr Uncertain significance ★ ⚠ same type
- CCN5 p.Ala72Thr Uncertain significance ★ ⚠ same type
- CCN5 p.Arg105Ser Uncertain significance ★ ⚠ same type
- CCN5 p.Arg215Trp Uncertain significance ★ ⚠ same type
- CCN5 p.Arg221His Uncertain significance ★ ⚠ same type
- CCN5 p.Arg229Cys 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/ccn5-p-pro84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown