Is MTM1 p.Arg520= (c.1560A>G) pathogenic?

MTM1 p.Arg520= (c.1560A>G) is classified Likely benign in MTM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). Very rare (popmax 0.000558%, nfe); Associated with X-linked myotubular myopathy.

What condition is associated with MTM1 p.Arg520= (c.1560A>G)?

MTM1 p.Arg520= (c.1560A>G) is associated with X-linked myotubular myopathy (ClinVar).

How common is MTM1 p.Arg520= (c.1560A>G) in the general population?

MTM1 p.Arg520= (c.1560A>G) is very rare (popmax 0.000558%, nfe) (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.Arg520=

c.1560A>G · rs138946055 · VCV1100717

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000558%, nfe)

Conditions

X-linked myotubular myopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.31	acceptor gain · deltas
Pangolin	Δ0.22	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.3	GERP -4.5, phastCons 1
Overall
CADD	15.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000558% European (non-Finnish) · 5/895,306 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000578% 7/1,211,680 alleles · very rare exomes 7/1,097,905 · genomes 0/113,775 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0042%	23,823
European (non-Finnish)grpmax	0.000558%	179,061

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg520=
Coding: c.1560A>G
MANE Select: NM_000252
dbSNP: rs138946055
Type: single nucleotide variant
Location: chrX:150663525 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 520: 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.Arg520Ter Pathogenic ★★ same residue
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

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-arg520 (accessed [today's date]).

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