Among the total of 23 SARM1 ARM domain and other N-terminal coding variants seen in patients and controls in the Project MinE DF1 and Answer ALS databases, we have identified a group of seven of the exclusively patient-associated variants – L223P, Δ229–235, Δ249–252, R267W, V331E, E340K and T385A SARM1 – as having very strong constitutive NADase GoF, with each being 10–20 times more active than WT SARM1. Here, SARM1 is linked to amyotrophic lateral sclerosis.