Is MECP2 p.Val324fs (c.970dup) pathogenic?

MECP2 p.Val324fs (c.970dup) is classified Pathogenic in MECP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). No gnomAD frequency available for this variant; Associated with severe neonatal-onset encephalopathy with microcephaly.

What condition is associated with MECP2 p.Val324fs (c.970dup)?

MECP2 p.Val324fs (c.970dup) is associated with severe neonatal-onset encephalopathy with microcephaly (ClinVar).

How common is MECP2 p.Val324fs (c.970dup) in the general population?

MECP2 p.Val324fs (c.970dup) is no gnomAD frequency available for this variant (gnomAD).

How is MECP2-related severe neonatal encephalopathy inherited?

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

MECP2 p.Val324fs

c.970dup · rs2148661854 · VCV1454385

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

severe neonatal-onset encephalopathy with microcephaly

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	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.4, 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.Val324fs
Coding: c.970dup
MANE Select: NM_001110792
dbSNP: rs2148661854
Type: Duplication
Location: chrX:154030893 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 324: a UniProt-annotated variant site (in rtt); the 'disordered' region

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

Disease context

severe neonatal-onset encephalopathy with microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MECP2-related severe neonatal encephalopathy (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

MECP2 p.Val324= Likely benign ★★★ same residue
MECP2 p.Gly250fs Pathogenic/Likely pathogenic ★★ same condition
MECP2 p.Lys245fs Pathogenic ★★ same condition
MECP2 p.Pro481fs Pathogenic/Likely pathogenic ★★ same condition
MECP2 p.Thr111fs Pathogenic ★★ same condition
MECP2 p.Glu226fs Pathogenic ★ same condition
MECP2 p.Glu444fs Pathogenic ★ same condition
MECP2 p.Leu394fs 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-val324fs (accessed [today's date]).

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