Maybe @thribs is thinking of Bizarro, but I'm pretty sure there's been a Bizarro Supergirl in the comics before.
There's been a Bizarro of pretty much everybody in the comics, but the original was basically a failed Superman clone, and that's the origin they used for the Bizarro Supergirl in the show, with no prior Bizarros having existed in its reality. So in that sense, they did gender-swap Bizarro #1.
More recently, they gender-swapped the second Toyman, Jack B. Nimball, into Jacqueline Nimball.