Of whom it was said, That in Isaac shall thy seed be called; - Genesis 21:12. A numerous posterity had been promised to him. It was there said expressly that this promise was not to be fulfilled through the son of Abraham, by the bondwoman Hagar, but through Isaac. Of course, it was implied that Isaac was to reach manhood, and yet notwithstanding this, and notwithstanding Abraham fully believed it, be prepared deliberately, in obedience to the divine command, to put him to death. The phrase "thy seed be called" means, that his posterity was to be named after Isaac, or was to descend only from him. The word "called" in the Scriptures is often equivalent to the verb "to be;" see Isaiah 56:7. To "name" or "call" a thing was the same as to say that it was, or that it existed. It does not mean here that his "spiritual" children were to be called or selected from among the posterity of Isaac, but that the posterity promised to Abraham would descend neither from Ishmael nor the sons of Keturah, but in the line of Isaac. This is a strong circumstance insisted on by the apostle to show the strength of Abraham's faith. It was shown not only by his willing hess to offer up the child of his old age - his only son by his beloved wife, but by his readiness, at the command of God, to sacrifice even him on whom the fulfillment of the promises depended.

Of whom it is said,.... That is, of Isaac, Abraham's own son, whom he offered up; or rather, "to whom it was said", as the Vulgate Latin and Syriac versions render it; that is, to Abraham, for to him was this said, Genesis 21:12
that in Isaac shall thy seed be called; that numerous natural seed of his, which should inherit the land of Canaan; and his special famous seed, the Messiah, to whom the promises were made; See Gill on Romans 9:7.

Of whom--rather as Greek "He (Abraham, not Isaac) TO whom it was said" [ALFORD]. BENGEL supports English Version. So Hebrews 1:7 uses the same Greek preposition, "unto," for "in respect to," or "of." This verse gives a definition of the "only-begotten Son" (Hebrews 11:17).
in Isaac shall thy seed be called-- (Genesis 21:12). The posterity of Isaac alone shall be accounted as the seed of Abraham, which is the heir of the promises (Romans 9:7).

In Isaac shall thy seed be called - From him shall the blessed seed spring. Genesis 21:12.