Trey is right insofar as the clause "who is smart" is non-parenthetical. In other words, the clause is needed to understand the sentence when a speaker has more than one sister. If the speaker has only one sister, then the clause is parenthetical, and a comma is needed.

The correct way to say this is: I have a sister who is smart. "Who is smart" is an adjective clause and does not need to be preceded by a comma. :)