Protein complex assembly often begins while at least one of the subunits is still in the process of being translated. When such cotranslational assembly occurs for homomeric complexes, made up of multiple copies of the same subunit, this will result in complexes whose subunits were translated off of the same mRNA in an allele-specific manner. It has therefore been hypothesised that cotranslational assembly may be able to counter the assembly-mediated dominant-negative effect, whereby the co-assembly of mutant and wild-type subunits “poison” the activity of a protein complex. Here, we address this, showing first that subunits that undergo cotranslational assembly are much less likely to be associated with autosomal dominant relative to recessive disorders. Moreover, we observe that subunits with dominant-negative disease mutations are significantly depleted in cotranslational assembly compared to those associated with loss-of-function mutations. Consistent with this, we also find that complexes with known dominant-negative effects tend to expose their interfaces late during translation, lessening the likelihood of cotranslational assembly. Finally, by combining protein complex properties with other protein-level features, we trained a computational model for predicting proteins likely to be associated with dominant-negative or gain-of-function molecular mechanisms, which we believe will be of considerable utility for protein variant interpretation.