Genetic dominance has long been considered as a qualitative reflection of interallelic interactions. Dominance arises from many multiple sources whose unifying theme is the existence of non‐linear relationships between the genotypic and phenotypic values. One of the clearest examples are dominant negative mutations (DNMs) in which a defective subunit poisons a macromolecular complex. Dominance can also be due to the presence of a heterozygous null allele, as is the case of haploinsufficiency. Dominance can also be influenced by epistatic (interloci) interactions. For instance, a pre‐existing genetic variant can make possible the expression of a pathogenic variant in a seemingly “dominant” fashion. Such interactions, which can make an individual more or less sensitive to a particular pathogenic variant, will also be discussed here.