This notes that they disabled reading config files in order to own life as the default setup. I assume that with more time it would be wise to try and fuzz as many configured options as possible as well?
But you are right, that the configuration can be part of the fuzzed input. It should be possible to take part of the data fed into Irssi by AFL and use that as the config file and then use the rest as the network traffic.
It might be a good idea to check the parser for bugs but these aren't real security issues.