Of the 14 different rare DHTKD1 variants identified here in 643 unrelated ALS cases, all were predicted to be deleterious according to at least one of four prediction tools, four variants were pathogenic according to the ACMG guidelines [18], eight variants were located in the E1_dh dehydrogenase domain of the DHTKD1 protein, two of which were loss-of-function variants predicted to truncate this important functional domain, and seven variants were detected more than once, providing in silico evidence for the pathogenicity of most of the DHTKD1 variants described here. The gene discussed is DHTKD1; the disease is amyotrophic lateral sclerosis.