Is MTMR2 p.Arg604= (c.1810C>A) pathogenic?

MTMR2 p.Arg604= (c.1810C>A) is classified Likely benign in MTMR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). Ultra-rare (popmax 0.02%, afr); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with MTMR2 p.Arg604= (c.1810C>A)?

MTMR2 p.Arg604= (c.1810C>A) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is MTMR2 p.Arg604= (c.1810C>A) in the general population?

MTMR2 p.Arg604= (c.1810C>A) is ultra-rare (popmax 0.02%, afr) (gnomAD).

MTMR2 p.Arg604=

c.1810C>A · rs138746296 · VCV1656693

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.59, phastCons 1
Overall
CADD	6.846	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/75,010 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00988%

Overall 0.00112% 18/1,613,084 alleles · ultra-rare exomes 8/1,460,896 · genomes 10/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	5,001
Remaining individualsnot grpmax-eligible	0.0032%	31,227
East Asian	0.00223%	44,872

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.Arg604=
Coding: c.1810C>A
MANE Select: NM_016156
dbSNP: rs138746296
Type: single nucleotide variant
Location: chr11:95835412 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 5 PDB

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

Disease context

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

Similar variants

MTMR2 p.Arg604Ter Conflicting classifications of pathogenicity ★ same residue
MTMR2 p.Arg604Gln Uncertain significance ★ ⚠ same residue
MTMR2 c.804+2T>G Likely pathogenic ★★ same condition
MTMR2 p.Arg162Ter Pathogenic ★★ same condition
MTMR2 p.Arg364Ter 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-arg604 (accessed [today's date]).

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