I made my own layout somewhat recently.
For me, it was worth it. I had discomfort which went away. What Dygma mentions about the pinky is definitely relevant, but realistically just one aspect of the bigger issue: contorting your wrist. I took active measures when I made my layout to avoid this. It is worth noting, though, that you can also do other things to help with that. You can try to change how you press keys, maybe try to unlearn bad habits, but it will only take you so far if the key really is out of comfortable reach.
I chose to design my own layout by moving the Qwerty US layout keys around for a couple of reasons, but mostly it was that then it’s contained to that keyboard. It’s compatible with almost everything, just plug it in. Some things like Remote Desktop will forward scan codes to the client OS such that you are subject to the client OS layout. If your custom layout is a hardware rearrangement of Qwerty US, that’s MUCH easier to deal with than if your layout is in OS interpretation of scan codes since it will almost certainly be easy to select Qwerty US on the target OS.
For learning the new layout, I just spent a bunch of time on Monkeytype in my spare time until it started to break my ability to type Qwerty. Then I switched full time. Took a few months before I stopped dreading typing in chats and started approaching my old Qwerty speeds in Monkeytype, then another few months until muscle memory started to actually match the feeling of familiarity of Qwerty before the switch. Now I’m surprisingly finding that I can almost touch type Qwerty again even though I very rarely use it. The brain is a strange thing.