My PC gradually developed a strange startup problem. At first, I could unplug the PSU, hold the power button for 15–45 seconds until the fans and LEDs briefly flashed, then reconnect the PSU and start the system. For about a week, leaving USB power enabled while the PC was off also let it start with a normal two-second press of the power button. Eventually the USB ports stopped receiving power and the system stopped responding entirely.
I tested the power button with a multimeter and also shorted the motherboard power pins directly, with no response. The PSU provides roughly 5V on the 5VSB line, and shorting PS_ON# to ground makes the PSU show a brief LED flicker, but it does not start the system. A second known-good PSU behaved identically.
I also tested with a minimal setup: motherboard, CPU, cooler, one RAM stick, 24-pin power, and EPS power, with the graphics card, storage, and other PCIe/SATA devices disconnected. With the CPU installed, the board was completely dead. With the CPU removed, the fans initially spun and the board showed signs of life. After replacing the CMOS battery and clearing CMOS, however, the board became completely dead even with the CPU removed. The old battery measured about 2.09V and the replacement measures about 3.32V. There is currently no fan movement, LED activity, or USB power, despite 5VSB being present.
The CPU pins look straight, and the system had worked for more than a year with a Ryzen 7 5800X, MSI X470 Gaming Pro, 32GB of DDR4, and an RTX 3080. The CPU had been overclocked with PBO, and the board has used several different CPUs, RAM kits, and GPUs over its lifetime. Does this testing point conclusively to a failed motherboard, or is there another important test I should perform before buying a replacement?
3 Answers
At this point the motherboard is the strongest suspect. One final check is to remove it from the case and bench-test only the board, CPU, cooler, one RAM stick, the 24-pin connector, and the EPS connector. Short the power pins directly with a screwdriver. If it is still completely unresponsive outside the case, replacing the motherboard is the sensible next step.
You have already ruled out most of the usual causes: the power switch, two power supplies, the 5VSB rail, extra components, and a case-related short. The earlier intermittent startup behavior followed by total loss of standby activity is very consistent with a failing motherboard power circuit.
For MSI AM4 boards, a single RAM stick should normally be installed in DIMM A2, which is the second slot away from the CPU socket. It probably is not the cause of a totally dead board, but it is worth using the recommended slot during testing.
I tried both the first and second slots and got exactly the same behavior, but thanks for pointing that out.

I repeated the minimal test on the bench and it is still completely dead. That pretty much confirms the motherboard is the problem. Thanks for the sanity check.