A-to-I RNA editing can lead to recoding of pre-mRNAs with profound functional consequences for the ensuing proteins. Here we show that complement component 1, q subcomponent-like 1 (C1QL1) undergoes RNA editing in vivo causing non-synonymous amino acid substitutions in human, mouse as well as zebrafish. The major editing site had previously been annotated as a single-nucleotide polymorphism in human, but our analysis reveals that post-transcriptional modification is the cause for the sequence variation. Remarkably, although editing of C1QL1 is conserved across vertebrate species, the predicted RNA secondary structure mediating editing involves different regions in zebrafish versus mammals.