Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_002055.5(GFAP):c.957G>A (p.Arg319=)

CA8608782

323611 (ClinVar)

Gene: GFAP (HGNC:2670)

Condition: Alexander disease (MONDO:0008752)

Inheritance Mode: Autosomal dominant inheritance

UUID: fea4bf5b-17f8-4e53-86d0-43efbb19ca8f

Approved on: 2026-08-18

Published on: 2026-08-18

HGVS expressions

NM_002055.5(GFAP):c.957G>A (p.Arg319=)

NM_002055.5:c.957G>A

NC_000017.11:g.44911406C>T

CM000679.2:g.44911406C>T

NC_000017.10:g.42988774C>T

CM000679.1:g.42988774C>T

NC_000017.9:g.40344300C>T

NG_008401.1:g.9141G>A

ENST00000253408.11:c.957G>A

ENST00000435360.8:c.957G>A

ENST00000253408.10:c.957G>A

ENST00000435360.7:c.957G>A

ENST00000585543.6:n.110G>A

ENST00000586127.6:n.1486G>A

ENST00000586793.6:c.907-85G>A

ENST00000587997.6:n.433G>A

ENST00000588735.3:c.957G>A

ENST00000591327.2:n.2111G>A

ENST00000592320.6:c.619-85G>A

ENST00000638281.1:c.957G>A

ENST00000638618.1:c.612G>A

ENST00000639277.1:c.957G>A

ENST00000640552.1:n.971G>A

ENST00000253408.9:c.957G>A

ENST00000376990.8:c.*356G>A

ENST00000435360.6:c.957G>A

ENST00000585543.5:n.110G>A

ENST00000586793.5:c.957G>A

ENST00000587997.5:c.433G>A

ENST00000588640.5:n.337G>A

ENST00000588735.1:c.83-3290G>A

ENST00000592320.5:c.619-85G>A

NM_001131019.2:c.957G>A

NM_001242376.1:c.957G>A

NM_002055.4:c.957G>A

NM_001363846.1:c.957G>A

NM_001131019.3:c.957G>A

NM_001242376.2:c.957G>A

NM_001242376.3:c.957G>A

NM_001363846.2:c.957G>A

Benign

BA1

Evidence Links 0

Expert Panel

Leukodystrophy and Leukoencephalopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Leukodystrophy and Leukoencephalopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GFAP Version 1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Leukodystrophy and Leukoencephalopathy VCEP

The c.1140C>T (NM_002055.5(GFAP)) variant in GFAP is a synonymous (silent) variant (p.Arg319=). The GrpMax filtering allele frequency in gnomAD v4.1.1 is 0.01557 from the African/African American genetic ancestry group (the lower threshold of the 95% CI of 1226/75062 alleles), which is higher than the ClinGen Leukodystrophy and Leukoencephalopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GFAP Version 1.0.0 threshold ≥ 0.01% for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as likely benign based on the ACMG/AMP criteria applied, as specified by the ClinGen Leukodystrophy and Leukoencephalopathy VCEP: BA1 (ClinGen Leukodystrophy and Leukoencephalopathy VCEP Specifications Version 1.0.0).

BA1

The GrpMax filtering allele frequency in gnomAD v4.1.0 is 0.01557 from the African/African American genetic ancestry group (the lower threshold of the 95% CI of 1226/75062 alleles), which is higher than the ClinGen Leukodystrophy and Leukoencephalopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GFAP Version 1.0.0 threshold ≥ 0.01% for BA1, and therefore meets this criterion (BA1).

Curation History

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