MECP2 p.Pro400=
c.1200A>C · rs797044732 · VCV197244
ClinGen expert panel — Rett and Angelman-like Disorders VCEP
Benign for Rett syndrome. Applied ACMG criteria (verbatim):
BS2 BP5_Strong BP7 BA1
Curation rationale (ClinGen, verbatim)
The highest population minor allele frequency of the p.Pro388= variant in MECP2 (NM_004992.3) in gnomAD v4.1 is 0.0004921 in the Middle Eastern population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0003) for BA1, and therefore meets this criterion (BA1). The p.Pro388= variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2). The p.Pro388= variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx) (BP5_Strong). The silent p.Pro388= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Pro388= variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP5_Strong, BP7).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -2.5 |
| Overall | ||
| CADD | 0.197 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0492% | 2,032 |
| Admixed American | 0.0213% | 4,687 |
| Finnishnot grpmax-eligible | 0.0207% | 4,839 |
| African / African-American | 0.0185% | 5,401 |
| Remaining individualsnot grpmax-eligible | 0.00819% | 12,209 |
| South Asian | 0.00367% | 27,245 |
| European (non-Finnish) | 0.00226% | 44,343 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- MECP2
- Protein
- p.Pro400=
- Coding
- c.1200A>C
- MANE Select
- NM_001110792
- dbSNP
- rs797044732
- Type
- single nucleotide variant
- Location
- chrX:154030664 (GRCh38)
- Structure
- AlphaFold pLDDT 57.25 · 11 PDB
- Residue 400
- 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.Pro400Leu Benign ★★★ same residue
- MECP2 p.Pro400Ser Benign ★★★ ⚠ same residue
- MECP2 p.Pro400Ala Benign/Likely benign ★★ ⚠ same residue
- MECP2 p.Pro400Thr Uncertain significance ★ ⚠ same residue
- MECP2 p.Pro400_Pro479del Uncertain significance ★★★ same residue
- MECP2 p.Pro400_Pro405del Likely benign ★★★ same residue
- MECP2 p.Pro400Ter Pathogenic ★★ same residue
- MECP2 p.Pro400_Gly440delinsGlnTer Pathogenic ★ same residue
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-pro400 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown