A global PCVA, in which all protein point charges are varied simultaneously, can be used as a simple indicator of the accuracy of the resulting QM/MM reaction energy as well as other properties of the active site, such as ligand charges. For the considered test cases we found that when comparing different QM regions, the sensitivity in a global PCVA is smaller for those QM regions that yield results closer to the best estimate obtained for the largest QM regions, i.e., the sensitivity generally decreases when approaching the limit of a full QM calculation. However, this only holds once the QM regions have reached a reasonable size and the correlation between the sensitivity in a global PCVA and the deviation from the best estimate is not always clear.