We simulate atmospheric fractionation in escaping planetary atmospheres using IsoFATE, a new open-source numerical model. We expand the parameter space studied previously to planets with tenuous atmospheres that exhibit the greatest helium and deuterium enhancement. We simulate the effects of extreme-ultraviolet-driven photoevaporation and core-powered mass loss on deuterium–hydrogen and helium–hydrogen fractionation of sub-Neptune atmospheres around G, K, and M stars. Our simulations predict prominent populations of deuterium- and helium-enhanced planets along the upper edge of the radius valley with mean equilibrium temperatures of ≈370 K and as low as 150 K across stellar types. We find that fractionation is mechanism dependent, so constraining He/H and D/H abundances in sub-Neptune atmospheres offers a unique strategy to investigate the origin of the radius valley around low-mass stars. Fractionation is also strongly dependent on retained atmospheric mass, offering a proxy for planetary surface pressure as well as a way to distinguish between desiccated enveloped terrestrials and water worlds. Deuterium-enhanced planets tend to be helium dominated and CH4 depleted, providing a promising strategy to observe HDO in the 3.7 μm window. We present a list of promising targets for observational follow-up.