Higuchi et al1 established FAT3 as a novel gene for autosomal-recessive axonal neuropathy, with robust functional support from Drosophila and mouse models. The work is important. I write to question one aspect of the interpretive framework: the authors classify FAT3-related disorder as a neuropathy with variable expressivity, yet their own data suggest a more coherent explanation. Patient 3, who carries the structurally mildest variants, both classified by the authors’ modeling as having only mild or negligible destabilizing effects, presents with the most severe and multisystem phenotype: congenital onset, respiratory failure, autonomic dysfunction, intestinal pseudo-obstruction, scoliosis, central hypomyelination, corpus callosum thinning, and ventriculomegaly.