Traditionally, substituents are described not by their intrinsic properties, but by their effect elsewhere in a molecule. However, the quantum theory of atoms in molecules (QTAIM) provides a route to intrinsic substituent descriptors. Ideally, these descriptors would exhibit minimal change as the local environment changes, and hence be considered transferable. Whether this is true is an open question. Here, we evaluated the transferability of QTAIM functional group descriptors for 117 functional groups in a series of 17 substrates to determine whether descriptors obtained using hydrogen as substrate are transferable. The functional group volume has a strong, consistent, linear relationship throughout. All other hydrogen-based group descriptors exhibit a relatively strong linear relationship with those in carbon-based substrates and a reasonable linear relationship with those in non-carbon-based substrates. Outliers are readily interpretable in terms of substrate induced functional group geometry changes. As expected, directional descriptors lying along the substituent-substrate axis are the least conserved.