A mutation that inserts or deletes one or two nucleotides is usually more harmful than a mutation that substitutes one base for another because -

A It changes one amino acid in the sequence of a protein

B it shifts the reading frame for the rest of the code causing many errors

C The codon consists of three nucleotides coding for an amino acid

D the chromosomes fail to separate resulting in trisomy 21

There is code for every amino acid consecutively present in mRNA.
These codes are read by the ribosome to form proteins.
If one or two nucleotides are deleted or inserted, It completely changes the patern of codes.
Hence it will read differently and form a non-functioning protein.

Hence, we can conclude that If one or two nucleotides are added or deleted they will cause a shift in change the reading frame result in many errors.

For more about frame-shift mutation refer to the link:

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