Is MTM1 p.Val247= (c.741C>T) pathogenic?

MTM1 p.Val247= (c.741C>T) is classified Benign in MTM1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-04). Ultra-rare (popmax 0.0947%, eas); Associated with X-linked myotubular myopathy.

What condition is associated with MTM1 p.Val247= (c.741C>T)?

MTM1 p.Val247= (c.741C>T) is associated with X-linked myotubular myopathy (ClinVar).

How common is MTM1 p.Val247= (c.741C>T) in the general population?

MTM1 p.Val247= (c.741C>T) is ultra-rare (popmax 0.0947%, eas) (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.Val247=

c.741C>T · rs374360983 · VCV1166510

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0947%, eas)

Conditions

X-linked myotubular myopathy

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 -8.6	GERP -4.5
Overall
CADD	0.518	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0947% East Asian · 32/33,788 alleles

Filtering AF 0.0689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0601%

Overall 0.00422% 51/1,208,991 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0947%	1,056
African / African-American	0.00525%	19,054
Remaining individualsnot grpmax-eligible	0.0021%	47,562
South Asian	0.00176%	56,819
European (non-Finnish)	0.00157%	63,875

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: MTM1
Protein: p.Val247=
Coding: c.741C>T
MANE Select: NM_000252
dbSNP: rs374360983
Type: single nucleotide variant
Location: chrX:150645745 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 247: 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 c.1644+1G>A Pathogenic ★★★ same condition
MTM1 p.Arg224Ter Pathogenic ★★★ same condition
MTM1 p.Arg69Cys Pathogenic ★★★ same condition
MTM1 p.Gln451= Likely pathogenic ★★★ same condition
MTM1 p.Glu404Lys Pathogenic ★★★ same condition
MTM1 p.Pro205Leu Pathogenic ★★★ same condition
MTM1 p.Trp230Arg Likely pathogenic ★★★ same condition
MTM1 p.Tyr192Cys 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/mtm1-p-val247 (accessed [today's date]).

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