Which of the Following Mutations Is Most Likely to Cause

Which of the following mutations is most likely to cause a phenotypic change?

A) a duplication of all or most introns
B) a large inversion whose ends are each in the same region between genes
C) a nucleotide substitution in an exon coding for a transmembrane domain
D) a single nucleotide deletion in an exon coding for an active site
E) a frameshift mutation one codon away from the 3' end of the nontemplate strand