**Core Concept**
Frameshift mutations occur due to insertions or deletions of nucleotides in a DNA sequence, leading to a shift in the reading frame of the genetic code. This type of mutation can result in the synthesis of a completely different protein or a non-functional protein product.

**Why the Correct Answer is Right**
Frameshift mutations occur when the number of nucleotides inserted or deleted is not a multiple of three, as this disrupts the reading frame of the genetic code. The genetic code is read in triplets of nucleotides (codons), and a change in the number of nucleotides can alter the amino acid sequence of the protein. If the number of nucleotides inserted or deleted is a multiple of three, the reading frame is not disrupted, and the mutation is not a frameshift mutation.

**Why Each Wrong Option is Incorrect**
**Option A:** A frameshift mutation can occur with the insertion or deletion of a single nucleotide, as this disrupts the reading frame.
**Option B:** Frameshift mutations can occur when the number of nucleotides inserted or deleted is not a multiple of three, not when it is.
**Option C:** A frameshift mutation can occur with the insertion or deletion of a large number of nucleotides, not just a small number.

**Clinical Pearl / High-Yield Fact**
Frameshift mutations are a common type of mutation that can lead to genetic disorders, and understanding the mechanism of frameshift mutations is crucial for understanding the pathophysiology of these disorders.

**Correct Answer: C.**