Accurate prediction of protein stability changes upon single-site variations (xcex94xcex94G) is important for protein design, as well as for our understanding of the mechanisms of genetic diseases. The performance of high-throughput computational methods to this end is evaluated mostly based on the Pearson correlation coefficient between predicted and observed data, assuming that the upper bound would be 1 (perfect correlation). However, the performance of these predictors can be limited by the distribution and noise of the experimental data. Here we estimate, for the first time, a theoretical upper-bound to the xcex94xcex94G prediction performances imposed by the intrinsic structure of currently available xcex94xcex94G data.