Meaningful Sequence requires that when the visual, CSS-driven order of a page differs from its underlying source-code order, the reading order that a screen reader announces still makes logical sense. A multi-column layout that looks fine visually can read completely out of order if the HTML was not structured to match.
This is typically caught by disabling CSS entirely and reading through the raw content order, or by navigating the page linearly with a screen reader, both of which quickly expose layouts where content jumps unpredictably between unrelated sections.