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Criteria Specification (CSpec) Registry is intended to provide access to the Criteria Specifications used and applied by ClinGen Variant Curation Expert Panels and biocurators in the classification of variants.

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Criteria Specification

ClinGen Glucose-6-phosphate dehydrogenase Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for G6PD Version 1.0
Description : Pathogenic variants in G6PD can result in two distinct clinical phenotypes that are defined by differences in the residual G6PD enzyme activity as well as the clinical propensity for chronic nonspherocytic hemolytic anemia (CNSHA). The World Health Organization (WHO) has established diagnostic criteria to categorize G6PD variants, with Class A variants in G6PD corresponding to variants that have a residual median G6PD activity of <20% and are associated with CNSHA. In contrast, Class B variants in G6PD correspond to variants that have a residual median G6PD activity of <45% and are not associated with CNSHA, but are associated with triggered acute hemolytic anemia (AHA). To accommodate these WHO diagnostic criteria, we recommend that when residual median G6PD activity measurements and other phenotypic data are available for a variant in G6PD, the appropriate MONDO ID is chosen to reflect the clinical phenotype associated with that variant. Specifically, we recommend classifying variants in G6PD using the following MONDO IDs: G6PD deficiency - MONDO:0005775 An X-linked genetic condition caused by alterations in the gene G6PD that result in moderately to severely decreased activity levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD). Most individuals with G6PD deficiency are asymptomatic throughout their life. Individuals with G6PD variants that cause G6PD deficiency are at risk for severe neonatal jaundice. These individuals are also at risk for acute hemolytic anemia in response to certain medication exposures, chemical exposures, infections, or consumption of fava beans. G6PD deficiency, with chronic non-spherocytic hemolytic anemia (CNSHA) - MONDO:0010480 An X-linked genetic condition caused by alterations in the gene G6PD that result in severely decreased activity levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD). Individuals with hemizygous or homozygous G6PD variants associated with chronic non-spherocytic hemolytic anemia (CNSHA) will clinically manifest CNSHA. Individuals with G6PD variants that cause CNSHA are also at risk for severe neonatal jaundice and acute exacerbation of their chronic hemolytic anemia in response to certain medication exposures, chemical exposures, infections, or consumption of fava beans.
Version : 1.0
Classification Rules In Prep
12/5/2025
19:03:14
Classification Rules Submitted
1/12/2026
12:21:40
Pilot Rules In Prep
1/30/2026
21:57:02
Pilot Rules Submitted
10/5/2025
01:20:11