A frameshift mutation typically has a more significant impact on protein structure than a substitution mutation. This is because a frameshift alters the reading frame of the genetic code, leading to a completely different and often nonfunctional protein due to changes in the entire amino acid sequence downstream of the mutation. In contrast, a substitution mutation changes only one amino acid, which may have a minor effect on protein function or structure, depending on the specific amino acid involved and its role in the protein.
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