Is MTMR2 p.Arg162Ter (c.484C>T) pathogenic?

MTMR2 p.Arg162Ter (c.484C>T) is classified Pathogenic in MTMR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-08). Very rare (popmax 0.000426%, nfe); Associated with Charcot-Marie-Tooth disease type 4B1.

What condition is associated with MTMR2 p.Arg162Ter (c.484C>T)?

MTMR2 p.Arg162Ter (c.484C>T) is associated with Charcot-Marie-Tooth disease type 4B1, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is MTMR2 p.Arg162Ter (c.484C>T) in the general population?

MTMR2 p.Arg162Ter (c.484C>T) is very rare (popmax 0.000426%, nfe) (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.Arg162Ter

c.484C>T · rs2496570033 · VCV2190463

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000426%, nfe)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.54	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 0.51, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000426% European (non-Finnish) · 5/1,174,888 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000311% 5/1,608,042 alleles · very rare exomes 5/1,455,826 · genomes 0/152,216 · 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: MTMR2
Protein: p.Arg162Ter
Coding: c.484C>T
MANE Select: NM_016156
dbSNP: rs2496570033
Type: single nucleotide variant
Location: chr11:95858617 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 5 PDB
Residue 162: a β-strand

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.Arg162Gln Uncertain significance ★ ⚠ same residue
MTMR2 c.804+2T>G Likely pathogenic ★★ same condition
MTMR2 p.Arg102Ter Pathogenic/Likely pathogenic ★★ same condition
MTMR2 p.Arg364Ter Pathogenic ★★ same condition
MTMR2 p.Gln590Ter Pathogenic ★★ same condition
MTMR2 p.Glu531Ter Pathogenic ★★ same condition
MTMR2 p.Glu574Ter Pathogenic/Likely pathogenic ★★ same condition
MTMR2 c.262+4C>T 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-arg162ter (accessed [today's date]).

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