Yes, I'm with @Scarab - this issue apparently returned, or a similar one was introduced. We are on SmarterMail Enterprise Version - 16.3.6649, and I use the same configuration for all my domains which includes both regular Websites as well as a SmarterMail Web instance.
To make testing easy, I added a text-file into the folder that I can access via all the sites I have tested. However, when I go through our Webmail site, I get 404.
Before, while I was still on SmarterMail 12, I got an authentication issue. So it may be a different issue now but I believe it's still appropriate to keep this here instead of opening a new thread.