R460C (p.Arg460Cys) variant of SPAST (Spastin)
R460C (p.Arg460Cys) in SPAST (Spastin) is a missense change. Clinical records from ClinVar, EBI, and UniProt describe it as pathogenic in the context of Hereditary spastic paraplegia; not provided; Hereditary spastic paraplegia 4. The available variant effect predictions contribute to a CATVariant prioritization score of 0.84 / 1. The record also includes population frequency data, published literature, and structural context.
R460C (p.Arg460Cys) variant details
- p.Arg460Cys
- rs878854990
- ClinGen CA10581968
- NCI-TCGA Cosmic COSV5951
- cosmic curated COSV59518
- Pathogenic
- Hereditary spastic paraplegia; not provided; Hereditary spastic paraplegia 4
- Missense
- Variant Prioritization Score for Impact Estimate 0.839
- REVEL 0.88
- AlphaMissense 0.98
- MetaLR 0.91
- MetaSVM 1.01
- CADD 29.20
- PolyPhen-2 1.00
- ClinVar: Pathogenic (Hereditary spastic paraplegia; not provided; Hereditary spastic)
- EBI: Pathogenic (in SPG4)
- UniProt: Pathogenic (in SPG4)
- Most common in the REMAINING population (allele frequency 0.00048)
- Structural context available
- Cited in: Two novel mutations in the spastin gene (SPG4) found by DHPLC mutation analysis. (PMID 15482961)
- Cited in: Novel and recurrent spastin mutations in a large series of SPG4 Italian families. (PMID 22960362)