Is MTM1 p.Pro586Ser (c.1756C>T) pathogenic?

MTM1 p.Pro586Ser (c.1756C>T) is classified Likely benign in MTM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-13). AlphaMissense: likely benign (0.0601); Very rare (popmax 0.00439%, amr); Associated with X-linked myotubular myopathy.

What condition is associated with MTM1 p.Pro586Ser (c.1756C>T)?

MTM1 p.Pro586Ser (c.1756C>T) is associated with X-linked myotubular myopathy (ClinVar).

How common is MTM1 p.Pro586Ser (c.1756C>T) in the general population?

MTM1 p.Pro586Ser (c.1756C>T) is very rare (popmax 0.00439%, amr) (gnomAD).

How is X-linked centronuclear myopathy inherited?

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

What do computational predictors say about MTM1 p.Pro586Ser (c.1756C>T)?

AlphaMissense predicts likely benign (score 0.0601) — an in-silico prediction, not a clinical call.

MTM1 p.Pro586Ser

c.1756C>T · rs782482838 · VCV2999874

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked myotubular myopathy

Computational evidence

Protein change
AlphaMissense	0.0601	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -1.8
Regional constraint	o/e 0.98	unconstrained · MANE · 7,999 bp · p 0.86 · regional, not allelic
Overall
CADD	0.321	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% Admixed American · 2/45,564 alleles

Filtering AF 0.000728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000272%

Overall 0.000248% 3/1,209,170 alleles · very rare exomes 2/1,098,164 · genomes 1/111,006 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00439%	22,782
African / African-American	0.00176%	56,901

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.Pro586Ser
Coding: c.1756C>T
MANE Select: NM_000252
dbSNP: rs782482838
Type: single nucleotide variant
Location: chrX:150671539 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 586: the 'disordered' region

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.Pro586= Likely benign ★★ 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-pro586ser (accessed [today's date]).

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