Stump the Guesser follows the life of fairground performer Johnny, who is hopelessly in love with his half-sister Sara. Unfortunately, societal norms and the taboo of incest make it extremely difficult for Johnny to pursue a relationship with her.
One day, after a particularly bad day at work, Johnny becomes fixated on the idea of disproving the theory of heredity. He believes that if he can prove that genetics do not determine a person's fate or behavior, then he and Sara can be together without fear of passing down any negative traits to their potential offspring.
He starts to conduct experiments and research, even enlisting the help of a geneticist. However, his obsession with his goal begins to consume him, and he becomes more and more isolated from the people around him, including Sara.
As Johnny starts to unravel and become more erratic, his determination to prove his theory becomes dangerous, and it jeopardizes his relationships with everyone he knows. The film examines the limits of love and the consequences of obsession while questioning the role of nature versus nurture.