I took one of my G21 Gen 5s out shooting yesterday (the one in the OP) along with a case of American Eagle 230gr FMJ to run through it (not all of it at once, mind you). I loaded the mag (fresh Gen 5 mag that had never had an issue before) to 12 rounds. On that first mag of the range session, it had the exact same weird malfunction detailed in the OP (again on the second-to-last round with the rear of the cartridge sticking down the magwell). This time I made sure to have my finger well away from the right side slide stop, and I was definitely not fatigued as it was the first mag of the day.
Not sure if it was me, I handed it off to a friend along with my AE ammo and let him shoot it for a bit while I focused on shooting my new shotgun. About 120 rounds later, it did the same thing to him. At that point I called it off as I didn't want to keep blowing through precious .45 ammo just to find out if it would keep doing it. I boxed the gun up and got out one of my low round count Gen 4 G21s to shoot instead. Shot 300 rounds through it without an issue, including using the same mag that had two stoppages in the Gen 5 shortly before. Also ran my USP 45 FS and HK45C for a couple hundred rounds each, also no issues.
At this point, that's such a weird jam to happen 3 times in less than 700 rounds with one G21 Gen 5, and also in another G21 Gen 5, I'm not thinking it's user error or a series of defective OEM magazines. It happened with Lawman and American Eagle 230gr. I have had consistently reliable function with those brands in particular for tens of thousands of rounds in other pistols, including other G21s of previous gens. It's frustrating because it's relatively infrequent and random, going sometimes hundreds of rounds before doing it again, and I can't begin to diagnose what the issue is. It's always the exact same type of stoppage, and on the 2nd to last round of a mag. It's even more frustrating because the G21 Gen 5 shoots so damn well. Not really sure what to do at this point, but no matter how you slice it, .45 is an expensive round to keep resetting round counts after stoppages to see if it can get to 1k rounds without a stoppage, only for it to keep happening.
EDIT: Regarding differences between the Gen 5 and Gen 4 G21, comparing the RSA's side by side, the Gen 5 is noticeably longer than the Gen 4's. This likely contributes to the heavier spring weight, as well as how the Gen 5 is softer shooting than the Gen 4.