Is MECP2 p.Pro314Arg (c.941C>G) pathogenic?

MECP2 p.Pro314Arg (c.941C>G) is classified Pathogenic/Likely pathogenic in MECP2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). AlphaMissense: likely pathogenic (0.9929); Absent from gnomAD v4.1; Associated with severe neonatal-onset encephalopathy with microcephaly.

What condition is associated with MECP2 p.Pro314Arg (c.941C>G)?

MECP2 p.Pro314Arg (c.941C>G) is associated with severe neonatal-onset encephalopathy with microcephaly, Rett syndrome (ClinVar).

How common is MECP2 p.Pro314Arg (c.941C>G) in the general population?

MECP2 p.Pro314Arg (c.941C>G) is absent from gnomAD v4.1 (gnomAD).

How is MECP2-related severe neonatal encephalopathy inherited?

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

What do computational predictors say about MECP2 p.Pro314Arg (c.941C>G)?

AlphaMissense predicts likely pathogenic (score 0.9929) — an in-silico prediction, not a clinical call.

MECP2 p.Pro314Arg

c.941C>G · rs61749723 · VCV143737

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9929 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

severe neonatal-onset encephalopathy with microcephaly

Computational evidence

Protein change
AlphaMissense	0.9929	likely pathogenic ✓ concordant with ClinVar
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -8.76	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.55	unconstrained · MANE · 1,052 bp · p 2.6e-22 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P302R vs ClinVar P314R) — verify the residue.

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.Pro314Arg
Coding: c.941C>G
MANE Select: NM_001110792
dbSNP: rs61749723
Type: single nucleotide variant
Location: chrX:154030923 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 302 UniProt numbering: the 'interaction with ncor2' region; a UniProt-annotated variant site (in rtt); the 'interaction with tbl1xr1' 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 p.Pro314Leu Pathogenic ★★★ ⚠ same residue
MECP2 p.Pro314Ala Pathogenic ★★ ⚠ same residue
MECP2 p.Pro314His Pathogenic ★★ ⚠ same residue
MECP2 p.Pro314Ser Pathogenic/Likely pathogenic ★★ ⚠ same residue
MECP2 p.Pro314= Benign/Likely benign ★★ same residue
MECP2 p.Pro314Thr Likely pathogenic ★ ⚠ same residue
MECP2 c.414-3C>G Pathogenic ★★★ same condition
MECP2 c.62+1G>A 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-pro314arg (accessed [today's date]).

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