MECP2 p.Val324=
c.972C>T · rs398124188 · VCV95207
ClinGen expert panel — Rett and Angelman-like Disorders VCEP
Likely Benign for Rett syndrome. Applied ACMG criteria (verbatim):
PM2_Supporting BS2_Supporting BP7 BP4
Curation rationale (ClinGen, verbatim)
Computational analysis prediction tools suggest that the p.Val312= variant in MECP2 (NM_004992) does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). The silent p.Val312= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). The p.Val312= variant is observed in at least 1 unaffected individual (GeneDx-internal database) (BS2_Supporting). The p.Val312= variant in MECP2 is absent from gnomAD (PM2_Supporting). In summary, the p.Val312= variant meets the criteria to be classified as Likely Benign. Although there are both pathogenic and benign types of evidence for this variant, the pathogenic evidence is not considered inconsistent with the final classification. ACMG/AMP criteria applied, as specified by the ClinGen Rett/Angelman-like expert panel: (BP4, BP7, BS2_Supporting, PM2_Supporting).
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 -0.03 | GERP -2.8, phastCons 0.42 |
| Overall | ||
| CADD | 1.685 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
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.Val324=
- Coding
- c.972C>T
- MANE Select
- NM_001110792
- dbSNP
- rs398124188
- Type
- single nucleotide variant
- Location
- chrX:154030892 (GRCh38)
- Structure
- AlphaFold pLDDT 57.25 · 11 PDB
- Residue 324
- 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.Val324fs Pathogenic ★ 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
- MECP2 p.Arg127His Pathogenic ★★★ same condition
- MECP2 p.Arg145Cys 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-val324 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown