Spondyloperipheral dysplasia: genes and variants

Genes linked to Spondyloperipheral dysplasia

• COL2A1: Collagen alpha-1(II) chain

  It provides the principal fibrillar collagen framework of cartilage and is also important in the vitreous and inner ear. Pathogenic variants cause a broad type II collagenopathy spectrum including Stickler syndrome, spondyloepiphyseal dysplasia, and severe skeletal dysplasias.

  13 disease-causing and 12 uncertain variants in COL2A1 are linked to Spondyloperipheral dysplasia.

Known disease-causing variants in Spondyloperipheral dysplasia

Which prediction tools work for Spondyloperipheral dysplasia

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• AlphaMissense: 99 out of 100
• MutPred2: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 94 out of 100
• MetaLR: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• EVE: 92 out of 100

Same protein, different disease

• Spondyloepiphyseal dysplasia congenita is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloperipheral dysplasia variants (38 disease-causing).
• Achondrogenesis type II is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloperipheral dysplasia variants (34 disease-causing).
• Stickler syndrome is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloperipheral dysplasia variants (26 disease-causing).
• Spondyloepimetaphyseal dysplasia, Strudwick type is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloperipheral dysplasia variants (18 disease-causing).
• Connective tissue disorder is also caused by COL2A1 variants; they fall mostly in different places as the Spondyloperipheral dysplasia variants (15 disease-causing).

Diseases related to Spondyloperipheral dysplasia

• Spondyloepiphyseal dysplasia congenita, also linked to COL2A1
• Achondrogenesis type II, also linked to COL2A1
• Stickler syndrome, also linked to COL2A1
• Connective tissue disorder, also linked to COL2A1
• Spondyloepimetaphyseal dysplasia, Strudwick type, also linked to COL2A1
• Type 2 collagenopathy, also linked to COL2A1
• Fetal anomalies with a likely genetic cause, also linked to COL2A1
• Spondyloepiphyseal dysplasia, Stanescu type, also linked to COL2A1
• Platyspondylic dysplasia, Torrance type, also linked to COL2A1
• Kniest dysplasia, also linked to COL2A1
• Stickler syndrome, type I, nonsyndromic ocular, also linked to COL2A1
• Paediatric disorders, also linked to COL2A1

Frequently asked questions

Which genes are linked to Spondyloperipheral dysplasia?

In CATVariant, Spondyloperipheral dysplasia is linked to 1 analyzed protein: COL2A1 (Collagen alpha-1(II) chain).

How many genetic variants are linked to Spondyloperipheral dysplasia?

29 variants: 13 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 12 are of uncertain significance or have conflicting reports.

Which uncertain variants in Spondyloperipheral dysplasia look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Spondyloperipheral dysplasia?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 9 disease-causing and 9 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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