Allele alphaLELY is a common low-expression allele of the erythroid spectrin SPTA1 gene. It results in the aggravated expression of hereditary elliptocytosis due to SPTA1 gene mutations occurring in trans. Allele alphaLELY contains, in particular, mutations in introns 45 and 46, both in polypyrimidine tracts, and causes the partial skipping of exon 46. The corresponding six amino acids belong to the nucleation site where the dimerization process of spectrin begins. In this work we investigated the cause of exon 46 partial skipping. We made four types of constructs with or without the intron 45 mutation, and with or without intron 46 mutation. Intron 45 mutation by itself dramatically triggered partial skipping of exon 46. Intron 46 mutation had no effect by itself. It was not possible to assess whether it modulated, even to a very small extent, the activity of intron 45 mutation. Taken together, intron 45 mutation is the prevalent, if not the exclusive, determinant of the partial skipping of exon 46 in the transcript of allele alphaLELY.