**Core Concept**
Sickle cell anemia is a genetic disorder caused by a mutation in the HBB gene, which codes for the beta-globin subunit of hemoglobin. This mutation leads to the substitution of glutamic acid with valine at position 6 of the beta-globin chain, resulting in abnormal hemoglobin S (HbS).

**Why the Correct Answer is Right**
The mutation in sickle cell anemia is caused by a point mutation in the HBB gene, resulting in the substitution of glutamic acid with valine at position 6 of the beta-globin chain. This substitution occurs due to a T to A transition at the 20th codon position of the HBB gene, which codes for valine instead of glutamic acid. The abnormal hemoglobin S (HbS) polymerizes under low oxygen conditions, leading to the characteristic sickling of red blood cells and clinical manifestations of sickle cell anemia.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is not relevant to the mutation in sickle cell anemia.
**Option B:** The mutation in sickle cell anemia is not caused by a frameshift mutation.
**Option C:** The mutation in sickle cell anemia is not caused by a deletion of a nucleotide.

**Clinical Pearl / High-Yield Fact**
Sickle cell anemia is inherited in an autosomal recessive pattern, meaning that individuals must inherit two abnormal HBB genes (one from each parent) to express the disease. Carrier individuals who inherit one abnormal HBB gene are asymptomatic but can pass the mutation to their offspring.

**Correct Answer:** C.