Additional members of this genetic framework were identified when the low-frequency (0.01 < MAF < 0.05) pathological/deleterious genetic variants were analyzed with the low-frequency biallelic AHNAK2,GLI3, PTIRM1, and ZNF254 variants, warranting a closer look at their potentially important role in fALS as C9ORF72 genetic modifiers as well as their link to both neuromuscular disorders/ALS and cancer. This evidence concerns the gene GLI3 and amyotrophic lateral sclerosis.