Some of the most common MEFV mutations (M694V, M694I and M680I) are predicted as benign/non-deleterious by two such programmes, PolyPhen and SIFT, while having the most severe clinical consequences.17 18 In silico prediction for MEFV variants may be hampered by the fact that amino acids that cause human disease are often present as a wild-type allele in primates,19 but also by the incomplete understanding of the pathophysiological mechanisms underlying FMF. The gene discussed is MEFV; the disease is familial Mediterranean fever.