Is MECP2 p.Ala293= (c.879C>T) pathogenic?

MECP2 p.Ala293= (c.879C>T) is classified Benign/Likely benign in MECP2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-02). Rare (popmax 0.435%, sas); Associated with Inborn genetic diseases.

What condition is associated with MECP2 p.Ala293= (c.879C>T)?

MECP2 p.Ala293= (c.879C>T) is associated with Inborn genetic diseases, severe neonatal-onset encephalopathy with microcephaly, Rett syndrome (ClinVar).

How common is MECP2 p.Ala293= (c.879C>T) in the general population?

MECP2 p.Ala293= (c.879C>T) is rare (popmax 0.435%, sas) (gnomAD).

MECP2 p.Ala293=

c.879C>T · rs61750252 · VCV138191

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.435%, sas)

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 -6.5	GERP -2.8
Overall
CADD	0.068	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.435% South Asian · 247/56,831 alleles

Filtering AF 0.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.373%

Overall 0.0523% 633/1,209,919 alleles · rare exomes 568/1,098,010 · genomes 65/111,909 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.435%	230
African / African-American	0.126%	795
East Asian	0.0889%	1,125
Remaining individualsnot grpmax-eligible	0.0882%	1,134
Admixed American	0.0414%	2,415
European (non-Finnish)	0.0241%	4,144
Middle Eastern	0.023%	4,354
Ashkenazi Jewishnot grpmax-eligible	0.0227%	4,406
Finnishnot grpmax-eligible	0.00216%	46,374

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.Ala293=
Coding: c.879C>T
MANE Select: NM_001110792
dbSNP: rs61750252
Type: single nucleotide variant
Location: chrX:154030985 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 293: 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.Ala293Thr Benign ★★★ same residue
MECP2 p.Ala293Gly Uncertain significance ★ ⚠ same residue
MECP2 p.Ala293fs Pathogenic/Likely pathogenic ★★ same residue
MECP2 p.Ala293del 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

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-ala293 (accessed [today's date]).

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