Is MTMR2 p.Ser514fs (c.1537_1538dup) pathogenic?

MTMR2 p.Ser514fs (c.15371538dup) is classified Pathogenic in MTMR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-03-05). Very rare (popmax 0.00167%, amr); Associated with Charcot-Marie-Tooth disease type 4B1.

What condition is associated with MTMR2 p.Ser514fs (c.1537_1538dup)?

MTMR2 p.Ser514fs (c.1537_1538dup) is associated with Charcot-Marie-Tooth disease type 4B1, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is MTMR2 p.Ser514fs (c.1537_1538dup) in the general population?

MTMR2 p.Ser514fs (c.1537_1538dup) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Charcot-Marie-Tooth disease type 4B1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MTMR2 p.Ser514fs

c.1537_1538dup · rs1555057316 · VCV406679

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Charcot-Marie-Tooth disease type 4B1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.63	GERP -5.6, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,928 alleles

Overall 6.85e-05% 1/1,459,618 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.Ser514fs
Coding: c.1537_1538dup
MANE Select: NM_016156
dbSNP: rs1555057316
Type: Microsatellite
Location: chr11:95838148 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 5 PDB
Residue 514: the myotubularin phosphatase domain; an α-helix

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

Disease context

Charcot-Marie-Tooth disease type 4B1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4

For Charcot-Marie-Tooth disease type 4B1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

MTMR2 p.Ala629fs Pathogenic/Likely pathogenic ★★ same condition
MTMR2 p.Val154_Cys155insTer Pathogenic ★★ same condition
MTMR2 p.Arg257fs Likely pathogenic ★ same condition
MTMR2 p.Val487fs Pathogenic ★ same condition
MTMR2 p.Asp252del Uncertain significance ★ same condition
MTMR2 p.Glu617fs Uncertain significance ★ same condition
MTMR2 p.Ser514Gly Uncertain significance ★ ⚠ same residue
MTMR2 c.1387-13_1387-12del Likely benign ★ 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-ser514fs (accessed [today's date]).

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