It really depends on the tool. If you are configuring with NetworkManager, it does save configuration, but it does not use the native Debian configuration tools to do so. According to the Debian wiki
for NetworkManager, it will not manage networks that are in the interfaces file.
also does not modify the interfaces file.
Most distros do not even use that file, and most of the GUI utilities are distro independent. They use other daemons to do the actual work of bringing up an interface.