Is MECP2 p.Pro211Arg (c.632C>G) pathogenic?

MECP2 p.Pro211Arg (c.632C>G) is classified Likely benign in MECP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-05-08). AlphaMissense: ambiguous (0.3405); Very rare (popmax 0.00528%, sas); Associated with Inborn genetic diseases.

What condition is associated with MECP2 p.Pro211Arg (c.632C>G)?

MECP2 p.Pro211Arg (c.632C>G) is associated with Inborn genetic diseases, severe neonatal-onset encephalopathy with microcephaly (ClinVar).

How common is MECP2 p.Pro211Arg (c.632C>G) in the general population?

MECP2 p.Pro211Arg (c.632C>G) is very rare (popmax 0.00528%, sas) (gnomAD).

What do computational predictors say about MECP2 p.Pro211Arg (c.632C>G)?

AlphaMissense predicts ambiguous (score 0.3405) — an in-silico prediction, not a clinical call.

MECP2 p.Pro211Arg

c.632C>G · rs267608502 · VCV515481

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3405 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00528%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3405	ambiguous
REVEL	0.397	indeterminate
SaProt	LLR -7.25	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 1.55	unconstrained · MANE · 1,052 bp · p 2.6e-22 · regional, not allelic
Overall
CADD	23.1	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 P199R vs ClinVar P211R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00528% South Asian · 3/56,782 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000689%

Overall 0.00132% 16/1,209,672 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00528%	18,927
European (non-Finnish)	0.00145%	68,853

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.Pro211Arg
Coding: c.632C>G
MANE Select: NM_001110792
dbSNP: rs267608502
Type: single nucleotide variant
Location: chrX:154031232 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 199 UniProt numbering: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe neonatal-onset encephalopathy with microcephaly

Similar variants

MECP2 p.Pro211Ser Benign ★★★ same residue
MECP2 p.Pro211His Benign ★★ same residue
MECP2 p.Pro211Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
MECP2 p.Pro211= Likely benign ★ same residue
MECP2 p.Pro211Leu Likely benign ★ 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

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-pro211arg (accessed [today's date]).

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