Is MECP2 p.Ala2Val (c.5C>T) pathogenic?

MECP2 p.Ala2Val (c.5C>T) is classified Pathogenic/Likely pathogenic in MECP2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-04-02). No allele count reported in gnomAD v4.1 (AN 1,022,366); Associated with severe neonatal-onset encephalopathy with microcephaly.

What condition is associated with MECP2 p.Ala2Val (c.5C>T)?

MECP2 p.Ala2Val (c.5C>T) is associated with severe neonatal-onset encephalopathy with microcephaly, Rett syndrome (ClinVar).

How common is MECP2 p.Ala2Val (c.5C>T) in the general population?

MECP2 p.Ala2Val (c.5C>T) is no allele count reported in gnomAD v4.1 (AN 1,022,366) (gnomAD).

How is MECP2-related severe neonatal encephalopathy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MECP2 p.Ala2Val

c.5C>T · rs179363901 · VCV11845

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,022,366)

Conditions

severe neonatal-onset encephalopathy with microcephaly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.229	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.02, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 65 kb · p 0.54 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,022,366). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MECP2
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_001110792
dbSNP: rs179363901
Type: single nucleotide variant
Location: chrX:154097661 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 2: the 'disordered' region

Full MECP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe neonatal-onset encephalopathy with microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rett syndrome

For MECP2-related severe neonatal encephalopathy (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

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
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-ala2val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown