Is MECP2 p.Ala295= (c.885C>G) pathogenic?

MECP2 p.Ala295= (c.885C>G) is classified Benign/Likely benign in MECP2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-19). Rare (popmax 0.154%, afr); Associated with Inborn genetic diseases.

What condition is associated with MECP2 p.Ala295= (c.885C>G)?

MECP2 p.Ala295= (c.885C>G) is associated with Inborn genetic diseases, severe neonatal-onset encephalopathy with microcephaly, Rett syndrome (ClinVar).

How common is MECP2 p.Ala295= (c.885C>G) in the general population?

MECP2 p.Ala295= (c.885C>G) is rare (popmax 0.154%, afr) (gnomAD).

MECP2 p.Ala295=

c.885C>G · rs61750253 · VCV143711

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.154%, afr)

Conditions

Inborn genetic diseases

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 12	GERP 1.4, phastCons 1
Overall
CADD	10.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.154% African / African-American · 88/57,180 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.118%

Overall 0.0086% 104/1,209,994 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.154%	650
Remaining individualsnot grpmax-eligible	0.0189%	5,291
Admixed American	0.00872%	11,473
European (non-Finnish)	0.000335%	298,388

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.Ala295=
Coding: c.885C>G
MANE Select: NM_001110792
dbSNP: rs61750253
Type: single nucleotide variant
Location: chrX:154030979 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 295: the 'interaction with ncor2' region; a UniProt-annotated variant site (in rtt); the 'interaction with tbl1xr1' 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 Rett syndrome

Similar variants

MECP2 p.Ala295Asp Uncertain significance ★ ⚠ 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
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-ala295 (accessed [today's date]).

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