The comic version of Reign definitely stands out as non-human, with her dark black eyes and voluminous red hair.
We can confirm that the Supergirl version of the villainess will look quite different from her comic counterpart.
Supergirl supervillains tend to be able to blend in with the citizens of National City, and Reign as seen in the comics would definitely stand out in a crowd.
Her costume will be different, and given that Odette Annable will be a regular, I’m guessing that she won’t have the same voluminous hair, eerie black eyes, and skin tone as the alien from the pages of the comics.