Is MTM1 p.Ser365Phe (c.1094C>T) pathogenic?

MTM1 p.Ser365Phe (c.1094C>T) is classified Uncertain significance in MTM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.2009); Very rare (popmax 0.00219%, amr); Associated with MTM1-related disorder.

What condition is associated with MTM1 p.Ser365Phe (c.1094C>T)?

MTM1 p.Ser365Phe (c.1094C>T) is associated with MTM1-related disorder (ClinVar).

How common is MTM1 p.Ser365Phe (c.1094C>T) in the general population?

MTM1 p.Ser365Phe (c.1094C>T) is very rare (popmax 0.00219%, amr) (gnomAD).

What do computational predictors say about MTM1 p.Ser365Phe (c.1094C>T)?

AlphaMissense predicts likely benign (score 0.2009) — an in-silico prediction, not a clinical call.

MTM1 p.Ser365Phe

c.1094C>T · rs2040149346 · VCV2631415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2009 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

MTM1-related disorder

Computational evidence

Protein change
AlphaMissense	0.2009	likely benign
REVEL	0.411	indeterminate
SaProt	LLR -8.88	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 4	GERP 1.2, phastCons 1
Regional constraint	o/e 0.11	constrained · MANE · 111 bp · p 3.2e-06 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00219% Admixed American · 1/45,728 alleles

Overall 8.26e-05% 1/1,210,120 alleles · very rare exomes 0/1,098,187 · genomes 1/111,933 · joint denominator

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.Ser365Phe
Coding: c.1094C>T
MANE Select: NM_000252
dbSNP: rs2040149346
Type: single nucleotide variant
Location: chrX:150657861 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 365: the myotubularin phosphatase domain

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

Disease context

MTM1-related disorder

Similar variants

MTM1 p.Arg421Gln Pathogenic/Likely pathogenic ★★ same condition
MTM1 p.Pro179Ser Pathogenic/Likely pathogenic ★★ same condition
MTM1 p.Tyr397Cys Pathogenic/Likely pathogenic ★★ same condition
MTM1 p.Tyr51Ter Pathogenic/Likely pathogenic ★★ same condition
MTM1 p.Ser527Asn Uncertain significance ★ ⚠ same condition
MTM1 p.Glu48Ter Pathogenic same condition
MTM1 p.Thr382Ile Uncertain significance ⚠ same condition
MTM1 p.Asp25fs 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-ser365phe (accessed [today's date]).

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