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_001110792.2(MECP2):c.377G>C (p.Gly126Ala)

CA270359

143540 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: 9ddf71e8-5a4c-405f-8f52-47ab776f6a69

Approved on: 2026-08-24

Published on: 2026-10-01

HGVS expressions

NM_001110792.2:c.377G>C

NM_001110792.2(MECP2):c.377G>C (p.Gly126Ala)

NC_000023.11:g.154032243C>G

CM000685.2:g.154032243C>G

NC_000023.10:g.153297694C>G

CM000685.1:g.153297694C>G

NC_000023.9:g.152950888C>G

NG_007107.2:g.109885G>C

NG_007107.3:g.109861G>C

ENST00000303391.11:c.341G>C

ENST00000453960.7:c.377G>C

ENST00000303391.10:c.341G>C

ENST00000369957.5:c.*395G>C

ENST00000407218.5:c.377G>C

ENST00000453960.6:c.377G>C

ENST00000486506.5:n.2689G>C

ENST00000611468.1:c.329G>C

ENST00000619732.4:c.341G>C

ENST00000622433.4:c.329G>C

ENST00000628176.2:c.341G>C

NM_001110792.1:c.377G>C

NM_001316337.1:c.62G>C

NM_004992.3:c.341G>C

NM_001316337.2:c.62G>C

NM_001369391.2:c.62G>C

NM_001369392.2:c.62G>C

NM_001369393.2:c.62G>C

NM_001369394.1:c.62G>C

NM_001369394.2:c.62G>C

NM_001386137.1:c.-220G>C

NM_001386138.1:c.-220G>C

NM_001386139.1:c.-220G>C

NM_004992.4:c.341G>C

Likely Pathogenic

PP3 PM1 PM6 PM2_Supporting

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MECP2 Version 6.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Gly114Ala variant in MECP2 (NM_004992.4) has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with clinical features of Rett syndrome (RettBASE) (PM6). The p.Gly114Ala variant occurs in the well-characterized methyl-DNA binding (MBD) functional domain of the MECP2 gene (PM1). The p.Gly114Ala variant in MECP2 is absent from gnomAD v4.1 (PM2_Supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Gly114Ala variant in MECP2 is classified as Likely Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PM1, PM6, PM2_Supporting, PP3). (MECP2 Specifications v6.0; curation approved on 8/24/2026)

PP3

REVEL 0.956 Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).

PM1

The p.Gly114Ala variant occurs in the well-characterized methyl-DNA binding (MBD) functional domain of the MECP2 gene (PM1).

PM6

The p.Gly114Ala variant in MECP2 (NM_004992.4) has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with clinical features of Rett syndrome (RettBASE) (PM6).

PM2_Supporting

The p.Gly114Ala variant in MECP2 is absent from gnomAD v4.1 (PM2_Supporting).

Curation History

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