Is MECP2 p.Pro191= (c.573C>G) pathogenic?

MECP2 p.Pro191= (c.573C>G) is classified Benign in MECP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-06). Very rare (popmax 0.00217%, amr); Associated with severe neonatal-onset encephalopathy with microcephaly.

What condition is associated with MECP2 p.Pro191= (c.573C>G)?

MECP2 p.Pro191= (c.573C>G) is associated with severe neonatal-onset encephalopathy with microcephaly (ClinVar).

How common is MECP2 p.Pro191= (c.573C>G) in the general population?

MECP2 p.Pro191= (c.573C>G) is very rare (popmax 0.00217%, amr) (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.Pro191=

c.573C>G · rs782676768 · VCV1599193

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

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 6.5	GERP 1.3, phastCons 1
Overall
CADD	11.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00217% Admixed American · 1/46,120 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000743% 9/1,212,089 alleles · very rare exomes 9/1,098,209 · genomes 0/113,880 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0063%	15,885
Admixed Americangrpmax	0.00217%	46,120
South Asian	0.00175%	56,986
European (non-Finnish)	0.000447%	223,896

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro191=
Coding: c.573C>G
MANE Select: NM_001110792
dbSNP: rs782676768
Type: single nucleotide variant
Location: chrX:154031291 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 191: a DNA-binding region; 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

For MECP2-related severe neonatal encephalopathy (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

MECP2 p.Pro191Ala Uncertain significance ★★ ⚠ same residue
MECP2 p.Pro191Ser Uncertain significance ★★ ⚠ same residue
MECP2 p.Pro191Leu Uncertain significance ★ ⚠ 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

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-pro191 (accessed [today's date]).

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