G464S / G448E (numbering differences)

These substitutions (reported under slightly different residue numbering schemes in older literature) are associated with moderate to high increases in fluconazole MIC (ranges commonly reported 8–64-fold), particularly when found with other alterations.

Often raises voriconazole MICs appreciably (2–16-fold depending on study).

Seen in clinicp???al isolates and functional studies; effect size often depends on assay method and background. Some substitutions map to regions that influence heme pocket geometry and azole binding.


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