Is MTMR2 p.Val349Phe (c.1045G>T) pathogenic?

MTMR2 p.Val349Phe (c.1045G>T) is classified Uncertain significance in MTMR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). AlphaMissense: ambiguous (0.3668); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MTMR2 p.Val349Phe (c.1045G>T)?

MTMR2 p.Val349Phe (c.1045G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MTMR2 p.Val349Phe (c.1045G>T) in the general population?

MTMR2 p.Val349Phe (c.1045G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MTMR2 p.Val349Phe (c.1045G>T)?

AlphaMissense predicts ambiguous (score 0.3668) — an in-silico prediction, not a clinical call.

MTMR2 p.Val349Phe

c.1045G>T · VCV3296685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3668 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3668	ambiguous
REVEL	0.541	indeterminate
SaProt	LLR -7.20	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -1.1, phastCons 0.009
Regional constraint	o/e 0.74	unconstrained · MANE · 47 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	21.2	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 8.48e-05% European (non-Finnish) · 1/1,179,806 alleles

Overall 6.84e-05% 1/1,461,564 alleles · very rare

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: MTMR2
Protein: p.Val349Phe
Coding: c.1045G>T
MANE Select: NM_016156
Type: single nucleotide variant
Location: chr11:95847848 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 5 PDB
Residue 349: the myotubularin phosphatase domain; a β-strand

Full MTMR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTMR2 p.Glu531Ter Pathogenic ★★ same condition
MTMR2 p.Ala397Gly Uncertain significance ★★ ⚠ same condition
MTMR2 p.Ala633Thr Uncertain significance ★★ ⚠ same condition
MTMR2 p.Arg119Trp Uncertain significance ★★ same condition
MTMR2 p.Arg233Gln Uncertain significance ★★ ⚠ same condition
MTMR2 p.Arg440Gln Uncertain significance ★★ ⚠ same condition
MTMR2 p.Arg621Ter Uncertain significance ★★ same condition
MTMR2 p.Arg62Lys Uncertain significance ★★ ⚠ 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/mtmr2-p-val349phe (accessed [today's date]).

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