Is MTM1 p.Pro179Ser (c.535C>T) pathogenic?

MTM1 p.Pro179Ser (c.535C>T) is classified Pathogenic/Likely pathogenic in MTM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-02). AlphaMissense: likely pathogenic (0.7731); Absent from gnomAD v4.1; Associated with MTM1-related disorder.

What condition is associated with MTM1 p.Pro179Ser (c.535C>T)?

MTM1 p.Pro179Ser (c.535C>T) is associated with MTM1-related disorder, X-linked myotubular myopathy, centronuclear myopathy (ClinVar).

How common is MTM1 p.Pro179Ser (c.535C>T) in the general population?

MTM1 p.Pro179Ser (c.535C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTM1 p.Pro179Ser (c.535C>T)?

AlphaMissense predicts likely pathogenic (score 0.7731) — an in-silico prediction, not a clinical call.

MTM1 p.Pro179Ser

c.535C>T · rs587783832 · VCV158978

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7731 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MTM1-related disorder

Computational evidence

Protein change
AlphaMissense	0.7731	likely pathogenic ✓ concordant with ClinVar
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -11.26	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 65 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	24.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MTM1
Protein: p.Pro179Ser
Coding: c.535C>T
MANE Select: NM_000252
dbSNP: rs587783832
Type: single nucleotide variant
Location: chrX:150641275 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 179: the myotubularin phosphatase domain; a UniProt-annotated variant site (in cnmx; mild)

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

Disease context

MTM1-related disorder

Also linked: X-linked myotubular myopathy centronuclear myopathy

Similar variants

MTM1 p.Pro179Thr 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-pro179ser (accessed [today's date]).

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