Final answer:
A single base substitution mutation is least likely to be harmful when it results in a synonymous codon that specifies the same amino acid, due to the redundancy of the genetic code, particularly at the wobble position.
Step-by-step explanation:
A single base substitution mutation is least likely to be deleterious when the single base change results in a codon that specifies the same amino acid as the original codon. This is often due to the redundancy in the genetic code, where the third base of a codon, known as the wobble base, may vary without altering the amino acid that is incorporated into the protein.
Contrastingly, a base change that results in an amino acid substitution that alters the tertiary structure of the protein or at the active site of an enzyme, or one that creates a stop codon, is more likely to be deleterious. These changes can lead to significant impacts on the protein's function or even result in premature termination of protein synthesis.