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.800G>C (p.Arg267Pro)

CA415171753

2229884 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: 6708388a-56c1-4c91-8b7f-c85de294d2ad

Approved on: 2026-01-28

Published on: 2026-03-31

HGVS expressions

NM_001110792.2(MECP2):c.800G>C (p.Arg267Pro)

NM_001110792.2:c.800G>C

NC_000023.11:g.154031064C>G

CM000685.2:g.154031064C>G

NC_000023.10:g.153296515C>G

CM000685.1:g.153296515C>G

NC_000023.9:g.152949709C>G

NG_007107.2:g.111064G>C

NG_007107.3:g.111040G>C

ENST00000303391.11:c.764G>C

ENST00000453960.7:c.800G>C

ENST00000637917.1:c.66-128G>C

ENST00000303391.10:c.764G>C

ENST00000407218.5:c.*136G>C

ENST00000453960.6:c.800G>C

ENST00000619732.4:c.764G>C

ENST00000622433.4:c.752G>C

ENST00000628176.2:c.*136G>C

NM_001110792.1:c.800G>C

NM_001316337.1:c.485G>C

NM_004992.3:c.764G>C

NM_001316337.2:c.485G>C

NM_001369391.2:c.485G>C

NM_001369392.2:c.485G>C

NM_001369393.2:c.485G>C

NM_001369394.1:c.485G>C

NM_001369394.2:c.485G>C

NM_001386137.1:c.95G>C

NM_001386138.1:c.95G>C

NM_001386139.1:c.95G>C

NM_004992.4:c.764G>C

Pathogenic

PS4_Moderate PS2_Very Strong PM6 PM2_Supporting

PP3

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 5.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Arg255Pro variant in MECP2 (NM_004992.3) has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in at least 3 individuals with features of Rett syndrome (Ambry Genetics- internal database, GeneDx- internal database) (PS2_Very strong). The p.Arg255Pro variant in MECP2 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with features of Rett syndrome (GeneDx- internal database) (PM6). The p.Arg255Pro variant has been observed in 3 individuals with affected with a neurodevelopmental phenotype consistent with MECP2-related conditions (Labcorp Genetics (formerly Invitae)- internal database; Ambry Genetics- internal database) (PS4_moderate). The p.Arg255Pro variant in MECP2 is absent from gnomAD v4.1 (PM2_Supporting). Computational prediction analysis tools are inconclusive for this variant. In summary, the p.Arg255Pro variant in MECP2 is classified as Pathogenic based on the ACMG/AMP criteria (PS2_very-strong, PM6, PS4_moderate, PM2_Supporting). (MECP2 Specifications v.5.0; curation approved on 01/28/2026)

PS4_Moderate

The p.Arg255Pro variant has been observed in 3 individuals with affected with a neurodevelopmental phenotype consistent with MECP2-related conditions (Labcorp Genetics (formerly Invitae)- internal database; Ambry Genetics- internal database) (PS4_moderate).

PS2_Very Strong

The p.Arg255Pro variant in MECP2 has been reported as a de novo occurrence (biological parentage confirmed) in at least 2 individuals with features of Rett syndrome (Ambry Genetics- internal database) (PS2_Very strong).

PM6

The p.Arg255Pro variant in MECP2 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with features of Rett syndrome (GeneDx- internal database) (PM6).

PM2_Supporting

The p.Arg255Pro variant in MECP2 is absent from gnomAD v4.1 (PM2_Supporting).

PP3

REVEL = 0.617. Computational prediction analysis tools are inconclusive for this variant.

Curation History

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