All the DAAO rare variants with their corresponding ID and allele frequencies are presented in Table 1 and shown in Fig. 1B. Our integrated study including MD simulations and in silico approaches reveal that certain structural and dynamic attributes corresponding to the active site residues, an active site loop comprising residues 216–228 and binding with cofactor FAD, contribute to the plausible loss of enzymatic activity, thus likely to be predisposing the individuals carrying these variations to ALS. This evidence concerns the gene DAO and amyotrophic lateral sclerosis.