Yes, you can't avoid the pH lowering effect of adding calcium to wort, whether its in the mash or in the kettle. Sure, you can reserve some calcium from the mash and produce a decent pH in the tun, but when you add the rest of the calcium to boost the sulfate level, the kettle wort pH will be reduced. In a hoppy beer, that can take the edge off the bittering and hop expression.
If you are adding a bunch of gypsum to reach a high sulfate target and your starting water doesn't have much alkalinity, it can depress the mash or kettle pH below the desirable hoppy beer target of about 5.4. Adding a bit of lime or baking soda can correct that.
Thanks for the reply, Martin. Any insight as to why I'm getting wildly different results when inputting the exact same parameters into both Bru'n Water and Brewer's Friend? I do have a pH meter on order but the difference in predicted mash pH between the two has me completely stumped. I generally use Bru'n Water as my go-to but was double checking results with Brewer's Friend and was caught off guard. I'll spare the input details as I assume they're arbitrary given that they are consistent between programs?