Is MTM1 p.Ser13Phe (c.38C>T) pathogenic?

MTM1 p.Ser13Phe (c.38C>T) is classified Conflicting classifications of pathogenicity in MTM1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0988); Very rare (popmax 0.00674%, nfe); Associated with X-linked myotubular myopathy.

What condition is associated with MTM1 p.Ser13Phe (c.38C>T)?

MTM1 p.Ser13Phe (c.38C>T) is associated with X-linked myotubular myopathy (ClinVar).

How common is MTM1 p.Ser13Phe (c.38C>T) in the general population?

MTM1 p.Ser13Phe (c.38C>T) is very rare (popmax 0.00674%, nfe) (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.Ser13Phe (c.38C>T)?

AlphaMissense predicts likely benign (score 0.0988) — an in-silico prediction, not a clinical call.

MTM1 p.Ser13Phe

c.38C>T · rs144473998 · VCV1082470

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0988 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00674%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

X-linked myotubular myopathy

Computational evidence

Protein change
AlphaMissense	0.0988	likely benign
REVEL	0.514	indeterminate
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 65 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	23.3	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 0.00674% European (non-Finnish) · 59/875,579 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00486%

Overall 0.00505% 60/1,187,672 alleles · very rare exomes 55/1,076,169 · genomes 5/111,503 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00674%	14,840
Remaining individualsnot grpmax-eligible	0.00213%	46,846

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.Ser13Phe
Coding: c.38C>T
MANE Select: NM_000252
dbSNP: rs144473998
Type: single nucleotide variant
Location: chrX:150592652 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 13: a modified residue (phosphoserine); 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.Ser13= Uncertain significance 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-ser13phe (accessed [today's date]).

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