ACAN p.Pro713=
c.2139C>T · VCV4707095
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, 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 -2.5 | GERP -1.8 |
| Overall | ||
| CADD | 4.269 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00291%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0026%
Overall
0.00335%
54/1,612,256 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,797 |
| European (non-Finnish) | 0.00382% | 26,208 |
| Admixed American | 0.00334% | 29,897 |
| African / African-American | 0.00267% | 37,441 |
| South Asian | 0.0011% | 90,558 |
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
- ACAN
- Protein
- p.Pro713=
- Coding
- c.2139C>T
- MANE Select
- NM_001369268
- Type
- single nucleotide variant
- Location
- chr15:88851906 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 713
- the 'ks' region
Similar variants
- ACAN p.Pro713Ser Uncertain significance ★ ⚠ same residue
- ACAN c.1733-2A>G Likely pathogenic ★★ same type
- ACAN c.630-13G>A Pathogenic ★★ same type
- ACAN c.7302+1G>A Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Arg236Ter Pathogenic ★★ same type
- ACAN p.Arg386Ter Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Arg394Ter Pathogenic ★★ same type
- ACAN p.Arg675Ter 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/acan-p-pro713 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown