no changes
Edit:
AH! It works, but I lower the MTU to 1280
Why so low? Because of some QubesOS specials?
Where did you lower the MTU? For what interface in what qube?
Maybe you have another VPN before sys-vpn?
in sys-vpn, in the networkmanger.
ahhmm… suppose not 
anyway, thanks a lot, it works!
this is curious as this firewall rule should fix the MTU problems dynamically, without having to modify your VPN MTU. 
hmm… the rule is still there, I even restarted the sys-vpn
If I set MTU in the network-manager, in the special VPN-connection to automatic instead of 1280, the connection is dead.
If I turn off the VPN connection, I even can ping jumbo packets with 9000
MTU=1376 is the highest possibility
Get also a problem with another wireguard connection to another network (here with OPNsense WG-server).
It seems to have no matter what MTU I set on the client. If I connect, I can ping exactly for times with very bad speed (about 200ms) and then connection dies. If I just reconnect, I can send again 4 pings.
not sure, if it has something to do with the OPNsense
Edit:
false key setting was the problem on the laptop and not MTU: