Is MECP2 p.Pro314= (c.942C>G) pathogenic?

MECP2 p.Pro314= (c.942C>G) is classified Benign/Likely benign in MECP2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-24). Ultra-rare (popmax 0.0435%, afr); Associated with severe neonatal-onset encephalopathy with microcephaly.

What condition is associated with MECP2 p.Pro314= (c.942C>G)?

MECP2 p.Pro314= (c.942C>G) is associated with severe neonatal-onset encephalopathy with microcephaly, Rett syndrome (ClinVar).

How common is MECP2 p.Pro314= (c.942C>G) in the general population?

MECP2 p.Pro314= (c.942C>G) is ultra-rare (popmax 0.0435%, afr) (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.Pro314=

c.942C>G · rs61751438 · VCV143739

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0435%, afr)

Conditions

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 1	GERP -1, phastCons 1
Overall
CADD	6.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0435% African / African-American · 25/57,433 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00231% 28/1,210,687 alleles · ultra-rare exomes 17/1,098,222 · genomes 11/112,465 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0435%	2,297
Remaining individualsnot grpmax-eligible	0.0042%	23,813
European (non-Finnish)	0.000112%	895,263

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.Pro314=
Coding: c.942C>G
MANE Select: NM_001110792
dbSNP: rs61751438
Type: single nucleotide variant
Location: chrX:154030922 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 314: a UniProt-annotated variant site (in rtt)

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.Pro314Arg Pathogenic/Likely pathogenic ★★ ⚠ same residue
MECP2 p.Pro314His Pathogenic ★★ ⚠ same residue
MECP2 p.Pro314Ser Pathogenic/Likely pathogenic ★★ ⚠ 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-pro314 (accessed [today's date]).

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