SOD1 and amyotrophic lateral sclerosis: A further quarter of mutations are in the same or adjacent codons to mutations with proven pathogenicity and a ‘hot-spot’ argument for pathogenicity can be presented.22 Conversely, after 28 years of screening many thousands of ALS patients for SOD1 mutations, there are obvious cold-spot codons in SOD1 where few or no mutations have been reported in ALS (or controls).