If one wants to ask what something indicates. In other words, he or she wants to know what that specific thing is sign of. How can he/she ask that? Is it correct to say Of what is it a sign? What are other possible ways to ask such a question?
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1I think it is uncommon to use the construction "Of what is it a sign?". It may even be grammatically incorrect. This sort of construction tends to be used when disbelief, disdain, or incredulity about the subject is present in the speaker, and is usually spoken with a retort-like tone. More commonly, "What is it a sign of?" is used instead; this has a more neutral inquisitive tone. – psosuna Sep 13 '17 at 21:01
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2It is grammatically correct, but very formal. The usual way to say it is either "What is it a sign of?" or "What does it signify?". (Depending on the intended shade of meaning, "What does it mean?", "What does it symbolise?", "What does it represent?" are other possibilities.) – rjpond Sep 13 '17 at 21:22
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Highly relevant: When is it appropriate to end a sentence {with} a preposition?. – Edwin Ashworth Sep 13 '17 at 21:31
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Structurally speaking, it is grammatically correct. I presume it was so constructed to avoid ending in a preposition. However, the general consensus on that guideline seems to be to avoid applying it overzealously, at the expense of making prose awkward. See this Oxford Dictionaries article on the matter, for instance.
Simply asking What is it a sign of? would likely be sufficient, but if you are very concerned about the guideline on prepositions, you may change the question to What does it [verb]?
The verb could be something like indicate, portend, signify, demonstrate, show, denote, betoken, etc.
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