Which is caused when there is a permanent change to the sequence of a gene?
mutation
karyotype
mutagen
phenotype

Mutation

Explanation:

Mutations are changes in the genetic material of cells that occur in the base sequences of gene DNA, causing changes in their structures. Mutations can be of two types: Gene mutations and chromosomal mutations.

In gene mutations, a portion of the molecule sequences is altered, leading to a change in the synthesized protein. A known example of a gene mutation is sickle cell anemia, characterized by the alteration of red blood cells to make them resemble a sickle.  

In chromosomal mutations, changes occur in whole parts of a chromosome (structural chromosome changes) or changes in chromosome number (numeric chromosome changes). An example of chromosomal mutation is Down's syndrome, which affects chromosome 21 (trisomy) causing physical and intellectual complications.

Despite all that, mutations do not exist just to trigger problems, they guarantee the genetic variability of living beings.

Moreover, they are considered an important point for the evolution of species, because it is through them that adaptive characteristics emerge that ensures the natural selection of more adapted species.