Create a UNIQUE multicolumn index on (product_id, variant_id):
CREATE UNIQUE INDEX line_items_prod_var_idx ON line_items (product_id, variant_id);
However, this would allow multiple entries of (1, NULL) for (product_id, variant_id) because NULL values are not considered identical.
To make up for that, additionally create a partial UNIQUE index on product_id:
CREATE UNIQUE INDEX line_items_prod_var_null_idx ON line_items (product_id)
WHERE variant_id IS NULL;
This way you can enter (1,2), (1,3) and (1, NULL), but neither of them a second time. Also speeds up queries with conditions on one or both column.
Recent, related answer on dba.SE, almost directly applicable to your case: