Is MECP2 p.Asp29fs (c.86dup) pathogenic?

MECP2 p.Asp29fs (c.86dup) is classified Pathogenic in MECP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-10-09). No gnomAD frequency available for this variant; Associated with Rett syndrome.

What condition is associated with MECP2 p.Asp29fs (c.86dup)?

MECP2 p.Asp29fs (c.86dup) is associated with Rett syndrome (ClinVar).

How common is MECP2 p.Asp29fs (c.86dup) in the general population?

MECP2 p.Asp29fs (c.86dup) is no gnomAD frequency available for this variant (gnomAD).

How is Rett syndrome inherited?

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

MECP2 p.Asp29fs

c.86dup · rs267608416 · VCV143605

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Rett syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -3.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MECP2
Protein: p.Asp29fs
Coding: c.86dup
MANE Select: NM_001110792
dbSNP: rs267608416
Type: Duplication
Location: chrX:154032533 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 29: 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

For Rett syndrome (Orphanet):

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

Similar variants

MECP2 p.Gly250fs Pathogenic/Likely pathogenic ★★ same condition
MECP2 p.Gly264fs Pathogenic/Likely pathogenic ★★ same condition
MECP2 p.Leu33fs Pathogenic/Likely pathogenic ★★ same condition
MECP2 p.Lys245fs Pathogenic ★★ same condition
MECP2 p.Thr111fs Pathogenic ★★ same condition
MECP2 p.Thr412fs Likely pathogenic ★★ same condition
MECP2 c.*98dup Benign/Likely benign ★★ same condition
MECP2 p.Ala213fs 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-asp29fs (accessed [today's date]).

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