Is MTM1 p.Val445Ala (c.1334T>C) pathogenic?

MTM1 p.Val445Ala (c.1334T>C) is classified Uncertain significance in MTM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-14). AlphaMissense: likely pathogenic (0.5884); Absent from gnomAD v4.1.

How common is MTM1 p.Val445Ala (c.1334T>C) in the general population?

MTM1 p.Val445Ala (c.1334T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTM1 p.Val445Ala (c.1334T>C)?

AlphaMissense predicts likely pathogenic (score 0.5884) — an in-silico prediction, not a clinical call.

MTM1 p.Val445Ala

c.1334T>C · rs2522443665 · VCV2662330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5884 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5884	likely pathogenic
REVEL	0.88	moderately pathogenic-leaning
SaProt	LLR -11.05	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 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 5,629 bp · p 2.6e-06 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Val445Ala
Coding: c.1334T>C
MANE Select: NM_000252
dbSNP: rs2522443665
Type: single nucleotide variant
Location: chrX:150659737 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 445: the myotubularin phosphatase domain

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

Similar variants

MTM1 c.1644+1G>A Pathogenic ★★★ same type
MTM1 p.Arg224Ter Pathogenic ★★★ same type
MTM1 p.Arg69Cys Pathogenic ★★★ same type
MTM1 p.Gln451= Likely pathogenic ★★★ same type
MTM1 p.Glu404Lys Pathogenic ★★★ same type
MTM1 p.Pro205Leu Pathogenic ★★★ same type
MTM1 p.Trp230Arg Likely pathogenic ★★★ same type
MTM1 p.Trp230Cys Likely pathogenic ★★★ same type

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-val445ala (accessed [today's date]).

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