Not sure that is possible, DDR5 does not fit in a DDR4 slot, at least on PC-type slots.
I’ve never heard of a motherboard that accepts multiple ddr revisions on the same physical slots, but I guess I am willing to accept that it is theoretically possible. I’m just doubting that yours performs this magic.
Make sure the boot drive is the first drive in the boot list in the machines BIOS. The boot drive may not always come back up as the first drive in the list of drives and if the drive is not marked as the first drive you get the BIOS trying to boot from the wrong drive. This issue got me on an older board once after a reboot, but would boot from a power off state. I didn’t have the drive marked in BIOS as the boot drive.
As far as RAM, you may just have a bad module or a counterfeit module that fails under moderate load. Plenty of those out there now days.
As far as I know you can not swap DDR4 modules out for DDR5 modules or vice-versa. The DDR5 module and slot has a different pin layout than a DDR4 module and slot. Both modules have key notches to align them in the correct place in the motherboard’s DIMM slots but the key notches are in slightly different places. If stacked on top of each other, the key notch on the DDR5 module is positioned a bit more to the left, while the DDR4 is more to the right. The pin layout on a DDR5 RAM module is different compared to a DDR4 module and I don’t think it will fit in a DDR4 slot and if forced may fry the memory and the motherboard.
PC Mag says not compatible DDR4 vs DDR5
Yee - but there actually exist converters for it. Also some really old generations of motherboard have had both generations of memory slots in the past.
I was just expressing that I have doubt that it’d be the same situation for this build.
Is this it?
2 x DDR3 DIMM Slots
2 x DDR2 DIMM Slots
Oh, didn’t know about the difference in pin layouts between RAM generations, I thought that SO-DIMM was just SO-DIMM as for PCIe interface 
Shame on me, thanks for the references guys!
So I have to find another DDR5 RAM module to test for potential defects
Can your motherboard boot with a single dimm? 8Gb of RAM should let you install as it is the bare minimum per docs.
You just need to check your motherboard docs to see what slot configuration are allowed for RAM
Thanks a lot for your insights, it helps me a lot 
I tried removing everything from the boot list in the BIOS except my boot drive, but it still doesn’t show up if I reboot instead of starting from a power off state. Just to be sure to understand correctly, can it be a boot / efi flag issue or something like that?
Also, can the boot drive being in an external enclosure connected via USB be an issue?
As for the RAM it’s from Crucial, if that makes any difference in the defect probability.
As mentioned in my very first post, I have a Beelink EQ12 Pro so the config is pretty minimal: single RAM slot of 16GB DDR5.
I just put three drives in there according to a test from cnx-software, and put a SATA SSD in an external enclosure connected through USB as a boot drive.
Yes - though many have success depending on the enclosure they use. I’m wondering if reboot vs power off is doing something stupid for the USB enclosure? Like on a reboot it never actually turns off properly, while shutting the system off forces it to do so?
Well maybe! Any way to test that in mind? 
Without careful use of a multimeter & risking production hardware? Not really.
See if BIOS has an option to NOT keep USB powered on when system is shutdown. Maybe that brief second during reboot would power off the USB connection, then power it back on causing problems to magically go away? I can’t really speak to risks (if any) of doing this, because I’d assume that the SSD would have no pending reads/writes when you do a safe system shutdown for reboot.
Final outcome
Before tinkering with the BIOS settings to cut USB power during shutdown, I tried changing the external boot drive enclosure (which basically means a different SATA-USB adaptor), and… all good! Reboot works as expected now, no more non-found boot drive 
As mentioned, there is definitely a heat management issue with the RAM: memtest86 crashes with embedded cooling, whereas it succeeds 4 passes with “powerful homemade external cooling solution” (see earlier post if you don’t know what I’m referring to 
).
So, I will go with this and keep an eye on the RAM (any way to monitor RAM temp in the GUI?) to see if real-world use even comes close to the stress test situation.
Thanks a lot for the help, your guidelines and feedback guys 
Wonderful community here!