It might have been her patrilineal great-grandmother: but Queen Maria I MARRIED her paternal uncle, who became co-sovereign as King Pedro III. So I'm not sure if that example really counts: it might otherwise have been difficult for her to inherit the Portuguese throne in her own right.
The accession in 1688 of Queen Mary II of Great Britain (house of Stuart) doesn't really count, either, since that was a special case: her father (King James VII/II) was DEPOSED during the so-called Glorious Revolution -- and her half-brother (Prince James Francis, the Old Pretender) was DISPLACED in the succession. Parliament later confirmed her and her sister's claims on the throne by passing the 1701 Act of Settlement.
But it's interesting nonetheless to note that there were no other living male agnates in the house of Stuart, since their father had no surviving younger brother -- just as King Henry VIII of England (house of Tudor) had no surviving younger brother. Otherwise, it would have been extremely difficult for Mary I and Elizabeth I to become queens in their own right; ditto for Mary II and Anne.
We know about the Carlist wars that ensued in Spain, when in 1833 the sonless King Fernando VII died and was succeeded by his elder daughter, Queen Isabel II -- despite the presence of numerous male relatives in the house of Bourbon.
It seems that Victoria of the United Kingdom, in 1837, was the first queen regnant to succeed without context, despite having paternal uncles and cousins. As it was, the Duke of Cumberland (heir presumptive until 1840) had no need to contest his niece's claim on the British throne, since he had a throne to claim elsewhere -- the German kingdom of Hanover.
It's too bad that Infante Carlos of Spain couldn't land a throne elsewhere, like the other junior agnates (the duchy of Parma and the kingdom of the Two Sicilies) in the house of Bourbon ...
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