The make.conf behavior for USE_EXPAND variables is slightly different from make.defaults behavior in profiles. There has always been an expectation that you could set VIDEO_CARDS="foo" and have that disable all of the video_cards_* settings from the profile, as shown in examples here: https://wiki.gentoo.org/wiki/Xorg/Guide#make.conf In the implementation, the difference in behavior arises from special treatment of USE_EXPAND variables in the config.regenerate method, where it translates USE_EXPAND variable setting from make.defaults into USE settings (and there's no equivalent code for USE_EXPAND variable settings from make.conf): https://gitweb.gentoo.org/proj/portage.git/commit/?id=637a13355cf4cc2906e34b61606d31d62acc9fcc
