Since you know where Frank and Sally are buried, you probably know the death dates for both of them.You can obtain copies of their death certificates, which should show the names and birth locations of their respective set of parents.
Have you looked for Isaac on 1860 census, when Frank would be about 6 yrs old, and see if Frank is in the household of Isaac, maybe his son?
You also might want to check probate and land records for Isaac, see if Frank is an heir?If Isaac left a will he may name Frank and give relationship.If no will, then all heirs would have to sign off before any land could be sold.
You didn't give death date for Mildred, did she live long enough to be on the 1900 census?Check for Frank on 1900 census, see if Mildred lived with him and his family after death of her husband.It would state her relationship to Frank.
If you're looking for county in TN where Frank was born, have you checked Sistler's multi-volume set of early TN marriages for Isaac and Mildred's marriage?Not all counties are included, but if you could find their marriage that would give you a county in TN for further records to search, too.
Please forgive me if I made suggestions for things you've already tried.