MECP2 p.Ser372fs
c.1114_*2524del · VCV189644
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Rett syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP -0.17, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- MECP2
- Protein
- p.Ser372fs
- Coding
- c.1114_*2524del
- MANE Select
- NM_001110792
- Type
- Deletion
- Location
- chrX:154027843 (GRCh38)
- Structure
- AlphaFold pLDDT 57.25 · 11 PDB
- Residue 372
- a UniProt-annotated variant site (in rtt); the 'disordered' region
Disease context
Rett syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Rett syndrome (Orphanet):
- Inheritance
- X-linked dominant
- Onset
- Infancy
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- MECP2 p.Ser372Ter Pathogenic ★★ same residue
- MECP2 p.Gly281fs Pathogenic ★★★ same condition
- MECP2 p.Ile305_Ser362del Likely pathogenic ★★★ same condition
- MECP2 p.Val392fs Pathogenic ★★★ same condition
- MECP2 p.His380fs Uncertain significance ★★★ same condition
- MECP2 p.Leu394_Pro402del Uncertain significance ★★★ same condition
- MECP2 p.Pro400_Pro479del Uncertain significance ★★★ same condition
- MECP2 p.Glu406_Pro417del Likely benign ★★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mecp2-p-ser372fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown