Somatic evolution occurs in an organism when a mutant cell arises and outcompetes other cells. A genotype different from the inherited one can thereby dominate a population of cells. We studied two brothers sharing Wiskott Aldrich Syndrome (WAS), a primary immunodeficiency disease. The brothers, whose inherited allele codes for truncated WAS protein (WASP), have remarkably diverse populations of T cells carrying many somatic WASP alleles. All compensate for the inherited allele by restoring the missing domain. Evolutionary principles predict that whereas single somatic alleles reflect rare stochastic events, multiple somatic alleles indicate a deterministic process in that selection against the inherited defect is so strong that independent rare mutations reach detectable frequencies. Thus, the presence of multiple corrective alleles serves as a sign that the inherited allele harbors unique information. We conclude that the brothers’ truncated WASP confers a disadvantage above and beyond that associated with absence of functional WASP, probably by competitively inhibiting a protein that would otherwise have partial compensatory function. Selection in this case acts early enough in T cell maturation for compensating mutants to profit, but too late to eliminate the defective inherited allele. In this way, evaluation of the two brothers by evolutionary principles within the framework of population genetics has informed an otherwise mysterious clinical phenomenon.