MECP2 p.Val392=
c.1176G>A · rs201711454 · VCV138194
ClinGen expert panel — Rett and Angelman-like Disorders VCEP
Benign for Rett syndrome. Applied ACMG criteria (verbatim):
BS2 BS1 BP7
Curation rationale (ClinGen, verbatim)
The allele frequency of the p.Val380= variant in MECP2 is 0.018% in Latino sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Val380= variant is observed in at least 2 unaffected individuals (internal database) (BS2). The silent p.Val380= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Val380= variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.7 | GERP -3.1 |
| Overall | ||
| CADD | 0.168 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0443% | 2,260 |
| Remaining individualsnot grpmax-eligible | 0.0212% | 4,728 |
| East Asian | 0.00596% | 16,786 |
| European (non-Finnish) | 0.00404% | 24,755 |
| African / African-American | 0.0036% | 27,784 |
| South Asian | 0.00356% | 28,108 |
| Finnishnot grpmax-eligible | 0.00229% | 43,713 |
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.Val392=
- Coding
- c.1176G>A
- MANE Select
- NM_001110792
- dbSNP
- rs201711454
- Type
- single nucleotide variant
- Location
- chrX:154030688 (GRCh38)
- Structure
- AlphaFold pLDDT 57.25 · 11 PDB
- Residue 392
- a UniProt-annotated variant site (in rtt); the 'disordered' region
Disease context
Rett syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: severe neonatal-onset encephalopathy with microcephaly
For Rett syndrome (Orphanet):
- Inheritance
- X-linked dominant
- Onset
- Infancy
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- MECP2 p.Val392Met Benign ★★★ same residue
- MECP2 p.Val392fs Pathogenic ★★★ same residue
- MECP2 p.Val392_Pro411del Uncertain significance ★ same residue
- MECP2 c.414-3C>G Pathogenic ★★★ same condition
- MECP2 c.62+1G>A Pathogenic ★★★ same condition
- MECP2 c.62+2T>G Pathogenic ★★★ same condition
- MECP2 p.Ala143Asp Pathogenic ★★★ same condition
- MECP2 p.Ala291Val Likely pathogenic ★★★ ⚠ 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-val392 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown