Error 21916664 fires when you try to revise a multi-variation listing and the variation specifics don't match what's already published. eBay locks variation structure after the listing receives a sale.
You changed the variation axis (e.g., switched 'Size' to 'Length'), reordered variation specifics, or added a new variation specific that wasn't in the original listing. Once a listing has bids or sales, the variation structure is partially locked.