Is MTM1 p.Val324fs (c.969dup) pathogenic?

MTM1 p.Val324fs (c.969dup) is classified Pathogenic in MTM1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-18). No gnomAD frequency available for this variant; Associated with X-linked myotubular myopathy.

What condition is associated with MTM1 p.Val324fs (c.969dup)?

MTM1 p.Val324fs (c.969dup) is associated with X-linked myotubular myopathy (ClinVar).

How common is MTM1 p.Val324fs (c.969dup) in the general population?

MTM1 p.Val324fs (c.969dup) is no gnomAD frequency available for this variant (gnomAD).

How is X-linked centronuclear myopathy inherited?

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

MTM1 p.Val324fs

c.969dup · rs587783865 · VCV211539

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked myotubular myopathy

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 10 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, 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: MTM1
Protein: p.Val324fs
Coding: c.969dup
MANE Select: NM_000252
dbSNP: rs587783865
Type: Duplication
Location: chrX:150649810 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 324: the myotubularin phosphatase domain

Full MTM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked myotubular myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked centronuclear myopathy (Orphanet):

Inheritance: X-linked recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (France)

Similar variants

MTM1 p.Val324= Likely benign ★ same residue
MTM1 p.Arg184fs Pathogenic ★★ same condition
MTM1 p.Gly177fs Pathogenic ★★ same condition
MTM1 p.Met317fs Pathogenic ★★ same condition
MTM1 c.137-11dup Benign/Likely benign ★★ same condition
MTM1 c.867_867+1dup Pathogenic ★ same condition
MTM1 p.Glu33Ter Pathogenic ★ same condition
MTM1 p.Ile44fs 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/mtm1-p-val324fs (accessed [today's date]).

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