>> I think your guess about fonts involved is right
>> because the problem disappears when the tab-line face
>> doesn't inherit from the 'variable-pitch' face.
>
> How can a face affect mouse-highlight?

Here is the minimal test case:

  (insert " " (propertize "TODO"
                          'face '(:inherit variable-pitch)
                          'mouse-face 'highlight))

that causes such effect after moving point over highlighted text
in fundamental-mode: