Accordingly, while the identification of pathogenic variants within the GLA gene is important to the diagnosis of FD, other questions have emerged regarding how to elucidate VUS and how to explore potential genotype–phenotype relationships to perform correct risk stratification [8, 13] While the “gold standard” to clarify if a novel pathogenic variant is likely pathogenic or likely benign includes in vitro GLA pathogenic variants expression assays, this is only available at specialized research laboratories [148]. Here, GLA is linked to Fabry disease.