Is MECP2 p.Pro411= (c.1233C>T) pathogenic?

MECP2 p.Pro411= (c.1233C>T) is classified Benign/Likely benign in MECP2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-26). Rare (popmax 0.316%, mid); Associated with Rett syndrome.

What condition is associated with MECP2 p.Pro411= (c.1233C>T)?

MECP2 p.Pro411= (c.1233C>T) is associated with Rett syndrome, severe neonatal-onset encephalopathy with microcephaly (ClinVar).

How common is MECP2 p.Pro411= (c.1233C>T) in the general population?

MECP2 p.Pro411= (c.1233C>T) is rare (popmax 0.316%, mid) (gnomAD).

How is Rett syndrome inherited?

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

MECP2 p.Pro411=

c.1233C>T · rs61753012 · VCV95188

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

rare (popmax 0.316%, mid)

Conditions

Rett syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.044	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.29	GERP -1.9, phastCons 0.011
Overall
CADD	3.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.316% Middle Eastern · 13/4,111 alleles

Filtering AF 0.187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.09% 1,082/1,201,784 alleles · rare exomes 994/1,093,493 · genomes 88/108,291 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.316%	316
Admixed American	0.115%	873
European (non-Finnish)	0.107%	934
Remaining individualsnot grpmax-eligible	0.078%	1,283
African / African-American	0.0196%	5,097
South Asian	0.0124%	8,075
Finnishnot grpmax-eligible	0.0094%	10,640
Ashkenazi Jewishnot grpmax-eligible	0.00455%	21,975

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.Pro411=
Coding: c.1233C>T
MANE Select: NM_001110792
dbSNP: rs61753012
Type: single nucleotide variant
Location: chrX:154030631 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 411: a UniProt-annotated variant site (in rtt); the 'disordered' region

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

Disease context

Rett syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe neonatal-onset encephalopathy with microcephaly

For Rett syndrome (Orphanet):

Inheritance: X-linked dominant
Onset: Infancy
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

MECP2 p.Pro411Ser Likely benign ★★★ same residue
MECP2 p.Pro411Leu Benign/Likely benign ★★ same residue
MECP2 p.Pro411fs 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-pro411 (accessed [today's date]).

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