Is MECP2 p.Pro263= (c.789C>T) pathogenic?

MECP2 p.Pro263= (c.789C>T) is classified Benign/Likely benign in MECP2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0391%, amr); Associated with History of neurodevelopmental disorder.

What condition is associated with MECP2 p.Pro263= (c.789C>T)?

MECP2 p.Pro263= (c.789C>T) is associated with History of neurodevelopmental disorder, severe neonatal-onset encephalopathy with microcephaly, Rett syndrome (ClinVar).

How common is MECP2 p.Pro263= (c.789C>T) in the general population?

MECP2 p.Pro263= (c.789C>T) is ultra-rare (popmax 0.0391%, amr) (gnomAD).

MECP2 p.Pro263=

c.789C>T · rs63582063 · VCV143686

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0391%, amr)

Conditions

History of neurodevelopmental disorder

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 -6.6	GERP -2.6
Overall
CADD	0.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0391% Admixed American · 18/45,999 alleles

Filtering AF 0.0252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.0135% 163/1,210,744 alleles · ultra-rare exomes 146/1,098,029 · genomes 17/112,715 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0391%	2,555
Middle Eastern	0.023%	4,355
Ashkenazi Jewishnot grpmax-eligible	0.0227%	4,405
African / African-American	0.0209%	4,788
South Asian	0.0141%	7,112
European (non-Finnish)	0.0122%	8,213
East Asian	0.0118%	8,439
Remaining individualsnot grpmax-eligible	0.0084%	11,907
Finnishnot grpmax-eligible	0.00428%	23,379

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.Pro263=
Coding: c.789C>T
MANE Select: NM_001110792
dbSNP: rs63582063
Type: single nucleotide variant
Location: chrX:154031075 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 263: the 'disordered' region

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

Disease context

History of neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe neonatal-onset encephalopathy with microcephaly Rett syndrome

Similar variants

MECP2 p.Pro263Arg Uncertain significance ★ ⚠ same residue
MECP2 p.Pro263Leu Likely benign ★ same residue
MECP2 p.Pro263fs Pathogenic ★ same residue
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

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-pro263 (accessed [today's date]).

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