ClinVar

Description

Variant summary: NEU1 c.544A>G (p.Ser182Gly) results in a non-conservative amino acid change located in the Sialidase domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.5e-05 in 241352 control chromosomes (gnomAD and publications). This frequency is not significantly higher than expected for a pathogenic variant in NEU1 causing Sialidosis (9.5e-05 vs 0.0011), allowing no conclusion about variant significance. c.544A>G has been reported in the literature in multiple individuals affected with Sialidosis (Chen_2006, Lukong_2000). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Chen_2006, Lukong_2000). The most pronounced variant effect results in <10% of normal activity. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.