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 0.85 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 6.967 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 100% | 1 |
| African / African-American | 99.8% | 1 |
| Middle Eastern | 99.7% | 1 |
| Admixed American | 99.6% | 1 |
| South Asian | 99.4% | 1 |
| Finnishnot grpmax-eligible | 99.3% | 1 |
| Remaining individualsnot grpmax-eligible | 98.8% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 98.4% | 1 |
| European (non-Finnish) | 98.4% | 1 |
| Amishnot grpmax-eligible | 97.7% | 1 |
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.Ala603=
- Coding
- c.1809T>C
- MANE Select
- NM_001369268
- dbSNP
- rs1568116
- Type
- single nucleotide variant
- Location
- chr15:88849514 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 603
- a disulfide bond; the 'g2-b'' region; the link 4 domain
Disease context
osteochondritis dissecans — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: spondyloepiphyseal dysplasia, Kimberley typespondyloepimetaphyseal dysplasia, aggrecan type
For Osteochondritis dissecans (Orphanet):
- Inheritance
- Not applicable
- Onset
- All ages
- Prevalence
- 1-5 / 10 000 (Europe)
Similar variants
- ACAN p.Ala603Thr Uncertain significance ★ ⚠ same residue
- ACAN c.1733-2A>G Likely pathogenic ★★ same condition
- ACAN p.Arg675Ter Pathogenic/Likely pathogenic ★★ same condition
- ACAN p.Asp2419Asn Likely pathogenic ★★ same condition
- ACAN p.Tyr164Ter Pathogenic ★★ same condition
- ACAN p.Ala171Val Uncertain significance ★★ ⚠ same condition
- ACAN p.Arg2503Gln Uncertain significance ★★ ⚠ same condition
- ACAN p.Arg2503Trp Uncertain significance ★★ same condition
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-ala603 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown