MECP2 p.Pro188=
c.564C>G · rs61754420 · VCV143612
ClinGen expert panel — Rett and Angelman-like Disorders VCEP
Likely Benign for Rett syndrome. Applied ACMG criteria (verbatim):
BS2 BP7 BP4
Curation rationale (ClinGen, verbatim)
The c.528C>G (p.Pro176=) variant in MECP2 (NM_004992.3) is observed in at least 2 unaffected individuals (internal database - Invitae) (BS2). The silent p.Pro176= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). The p.Pro176= variant in MECP2 is present in gnomAD v2.1.1 at a frequency of 0.003275% (no criteria met). In summary, the p.Pro176= variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP4, 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 7.3 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 10.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00424% | 23,560 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,609 |
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.Pro188=
- Coding
- c.564C>G
- MANE Select
- NM_001110792
- dbSNP
- rs61754420
- Type
- single nucleotide variant
- Location
- chrX:154031300 (GRCh38)
- Structure
- AlphaFold pLDDT 57.25 · 11 PDB
- Residue 188
- a DNA-binding region; 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.Pro188His Likely benign ★★★ ⚠ same residue
- MECP2 p.Pro188Leu Uncertain significance ★★ ⚠ same residue
- MECP2 p.Pro188Arg Benign/Likely benign ★★ same residue
- MECP2 p.Pro188Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- MECP2 p.Pro188Ala Likely benign ★ ⚠ 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
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-pro188 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown