MECP2 p.Arg465=
c.1393C>A · rs61753979 · VCV1114532
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
severe neonatal-onset encephalopathy with microcephaly
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 9.6 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 11.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- MECP2
- Protein
- p.Arg465=
- Coding
- c.1393C>A
- MANE Select
- NM_001110792
- dbSNP
- rs61753979
- Type
- single nucleotide variant
- Location
- chrX:154030471 (GRCh38)
- Structure
- AlphaFold pLDDT 57.25 · 11 PDB
- Residue 465
- a UniProt-annotated variant site (in rtt); the 'disordered' region
Disease context
severe neonatal-onset encephalopathy with microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor MECP2-related severe neonatal encephalopathy (Orphanet):
- Inheritance
- X-linked recessive
- Onset
- Infancy, Neonatal
Similar variants
- MECP2 p.Arg465Gln Likely benign ★★ same residue
- MECP2 p.Arg465Ter Pathogenic ★★ same residue
- MECP2 c.414-3C>G Pathogenic ★★★ same condition
- MECP2 c.62+1G>A Pathogenic ★★★ same condition
- MECP2 p.Ala291Val Likely pathogenic ★★★ ⚠ same condition
- MECP2 p.Arg127His Pathogenic ★★★ same condition
- MECP2 p.Arg145Cys Pathogenic ★★★ same condition
- MECP2 p.Arg145His 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-arg465 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown