Is MECP2 p.Ala290= (c.870C>T) pathogenic?

MECP2 p.Ala290= (c.870C>T) is classified Benign/Likely benign in MECP2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2025-12-15). Rare (popmax 0.279%, eas); Associated with Inborn genetic diseases.

What condition is associated with MECP2 p.Ala290= (c.870C>T)?

MECP2 p.Ala290= (c.870C>T) is associated with Inborn genetic diseases, severe neonatal-onset encephalopathy with microcephaly, Rett syndrome (ClinVar).

How common is MECP2 p.Ala290= (c.870C>T) in the general population?

MECP2 p.Ala290= (c.870C>T) is rare (popmax 0.279%, eas) (gnomAD).

MECP2 p.Ala290=

c.870C>T · rs61750248 · VCV143709

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

rare (popmax 0.279%, eas)

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 -2.8
Overall
CADD	0.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.279% East Asian · 94/33,749 alleles

Filtering AF 0.233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.216%

Overall 0.0359% 435/1,210,218 alleles · rare exomes 386/1,098,114 · genomes 49/112,104 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.279%	359
African / African-American	0.0506%	1,975
Middle Eastern	0.0459%	2,177
Remaining individualsnot grpmax-eligible	0.0441%	2,268
Admixed American	0.0327%	3,060
European (non-Finnish)	0.0285%	3,511
South Asian	0.0193%	5,169
Finnishnot grpmax-eligible	0.0151%	6,644
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,035

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.Ala290=
Coding: c.870C>T
MANE Select: NM_001110792
dbSNP: rs61750248
Type: single nucleotide variant
Location: chrX:154030994 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 290: 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.Ala290Thr Likely benign ★★ same residue
MECP2 p.Ala290Val Conflicting classifications of pathogenicity ★ ⚠ 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

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-ala290 (accessed [today's date]).

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