COL2A1 p.Arg586His
c.1757G>A · rs371440147 · VCV1386179
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2034 | likely benign |
|---|---|---|
| REVEL | 0.757 | pathogenic-leaning |
| SaProt | LLR -10.15 | damaging |
| ⇒ REVEL and SaProt call this damaging; AlphaMissense does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.62 | unconstrained · MANE · 21 kb · p 2.4e-45 · regional, not allelic |
| Overall | ||
| CADD | 29.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,336 |
| East Asian | 0.00223% | 44,884 |
| European (non-Finnish) | 0.00161% | 62,099 |
| South Asian | 0.0011% | 91,022 |
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
- COL2A1
- Protein
- p.Arg586His
- Coding
- c.1757G>A
- MANE Select
- NM_001844
- dbSNP
- rs371440147
- Type
- single nucleotide variant
- Location
- chr12:47985071 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 586
- the 'disordered' region; the 'triple-helical region' region
Disease context
Legg-Calve-Perthes disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Stickler syndrome type 1multiple epiphyseal dysplasia, Beighton typeplatyspondylic dysplasia, Torrance typeKniest dysplasiaspondyloepiphyseal dysplasia congenitaspondyloepimetaphyseal dysplasia, Strudwick typespondylometaphyseal dysplasia, 'corner fracture' typeachondrogenesis type IIspondyloperipheral dysplasiamild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritisspondyloepiphyseal dysplasia with metatarsal shorteningStickler syndrome, type I, nonsyndromic ocularspondyloepiphyseal dysplasia, Stanescu typevitreoretinopathy with phalangeal epiphyseal dysplasiaavascular necrosis of femoral head, primary, 1
For Legg-Calvé-Perthes disease (Orphanet):
- Inheritance
- Autosomal dominant, Multigenic/multifactorial
- Onset
- Childhood
Similar variants
- COL2A1 p.Arg586= Likely benign ★★ same residue
- COL2A1 c.1222-2A>G Pathogenic ★★ same condition
- COL2A1 c.1365+1G>A Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 c.1420-1G>A Pathogenic ★★ same condition
- COL2A1 c.1420-2A>G Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 c.1527+135G>A Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 c.1527+1G>A Likely pathogenic ★★ same condition
- COL2A1 c.1581+1G>A Likely pathogenic ★★ 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/col2a1-p-arg586his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown