Born in Kamishly, Syria on May 3, 1965, the youngest son of Mr. & Mrs. Issa Karim, His Eminence Metropolitan Mor Cyril Aphrem Karim lost his father at an early age and was raised, with the rest of his family, by his late and loving mother Khanema. He entered St. Ephrem's Theological Seminary in Atchaneh, Lebanon in 1977, following his primary schooling in Kamishly. In 1982, His Eminence served the Syriac Orthodox Archdiocese of Aleppo, Syria, for the next two years. From 1984 to 1988, Archbishop Karim pursued higher studies at the Coptic Theological Seminary in Cairo, Egypt, graduating with a Bachelor Degree of Divinity.

In 1985, Metropolitan Karim took the vows of a monk, and put himself in the service of the Church. He was ordained to the diaconate in Egypt, and later the same year, to the sacred priesthood in Kamishly. From 1988 to 1989, Mor Cyril served as both, the secretary of His Holiness, Moran Mor Zakka I Iwas, Syrian Orhtodox Patriarch of Antioch and all the East, and as a teacher at St. Ephrem's Theological Seminary in Damascus, Syria. In 1991, His Eminence entered St. Patrick's College in Maynooth, Ireland, where he received a License of Sacred Theology Degree, in 1992, and his Doctor of Divinity Degree in 1994, following a defense of his doctoral thesis on The Symbolism of the cross in early Syriac Christianity.

On Sunday, January 28, 1996, His Eminence was consecrated as Metropolitan and Patriarchal Vicar to the Archdiocese of the Syriac Orthodox Church for the Eastern United States, by His Holiness Patriarch Zakka I Iwas, at St. Mary 's Syriac Orthodox Church in Kamishly. Archbishop Mor Cyril Aphrem Karim arrived in The United States on March 2, 1996, and was officially installed to his position at St. Mark's Cathedral in Teaneck, New Jersey.

On March 21, 2014, His Holiness Patriarch Zakka I Iwas was called into his heavenly abode. Subsequently, the Holy Synod elected His Eminence Metropolitan Mor Cyril Aphrem Karim as the successor to the Holy Throne and the supreme head of the universal Syrian orthodox church. On May 29, 2014, in Damascus, Syria, His Eminence was consecrated as the 123rdsuccessor of St. Peter, with the name His Holiness Patriarch Ignatius Aphrem II.

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