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.1140C>T (p.Pro380=)

CA217126

66446 (ClinVar)

Gene: GFAP (HGNC:2670)

Condition: Alexander disease (MONDO:0008752)

Inheritance Mode: Autosomal dominant inheritance

UUID: 2381c78a-d14e-425b-993d-f0ef29f0d9e1

Approved on: 2026-08-18

Published on: 2026-08-18

HGVS expressions

NM_002055.5(GFAP):c.1140C>T (p.Pro380=)

NM_002055.5:c.1140C>T

NC_000017.11:g.44910646G>A

CM000679.2:g.44910646G>A

NC_000017.10:g.42988014G>A

CM000679.1:g.42988014G>A

NC_000017.9:g.40343540G>A

NG_008401.1:g.9901C>T

ENST00000253408.11:c.1140C>T

ENST00000435360.8:c.1140C>T

ENST00000253408.10:c.1140C>T

ENST00000435360.7:c.1140C>T

ENST00000585543.6:n.293C>T

ENST00000586125.2:c.75C>T

ENST00000586127.6:n.1669C>T

ENST00000588735.3:c.1140C>T

ENST00000591327.2:n.2294C>T

ENST00000591880.2:c.70C>T

ENST00000592320.6:c.717C>T

ENST00000638281.1:c.1140C>T

ENST00000638304.1:c.59C>T

ENST00000638488.1:n.81C>T

ENST00000638618.1:c.795C>T

ENST00000639042.1:c.77C>T

ENST00000639277.1:c.1140C>T

ENST00000639921.1:c.313C>T

ENST00000640552.1:n.1154C>T

ENST00000253408.9:c.1140C>T

ENST00000435360.6:c.1140C>T

ENST00000585543.5:n.293C>T

ENST00000586793.5:c.1140C>T

ENST00000588640.5:n.520C>T

ENST00000588735.1:c.83-2530C>T

ENST00000591880.1:c.6C>T

ENST00000592320.5:c.717C>T

NM_001131019.2:c.1140C>T

NM_001242376.1:c.1140C>T

NM_002055.4:c.1140C>T

NM_001363846.1:c.1140C>T

NM_001131019.3:c.1140C>T

NM_001242376.2:c.1140C>T

NM_001242376.3:c.1140C>T

NM_001363846.2:c.1140C>T

Benign

BP7 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.Pro380=) that is not predicted to impact the splice consensus sequence, nor the creation of a new splice site, and the nucleotide is not highly conserved with a phyloP score of <2.27 (BP7). The GrpMax filtering allele frequency in gnomAD v4.1.0 is 0.0001188 from the African/African American genetic ancestry group (the lower threshold of the 95% CI of 21/74738 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, BP7 (ClinGen Leukodystrophy and Leukoencephalopathy VCEP Specifications Version 1.0.0).

BP7

The c.1140C>T (p.Pro380=) variant is a synonymous (silent) variant that is not predicted to impact the splice consensus sequence, nor the creation of a new splice site, and the nucleotide is not highly conserved with a phyloP score of <2.27 (BP7).

BA1

The GrpMax filtering allele frequency in gnomAD v4.1.0 is 0.0001188 from the African/African American genetic ancestry group (the lower threshold of the 95% CI of 21/74738 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.