Is MTMR2 p.Arg586= (c.1756C>A) pathogenic?

MTMR2 p.Arg586= (c.1756C>A) is classified Benign in MTMR2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 9.05%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Charcot-Marie-Tooth disease.

What condition is associated with MTMR2 p.Arg586= (c.1756C>A)?

MTMR2 p.Arg586= (c.1756C>A) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4B1, Charcot-Marie-Tooth disease type 4 (ClinVar).

MTMR2 p.Arg586=

Q: How common is MTMR2 p.Arg586= (c.1756C>A) in the general population?

MTMR2 p.Arg586= (c.1756C>A) is common (popmax 9.05%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1756C>A · rs61735577 · VCV306536

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 9.05%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP -2.6, phastCons 0.87
Overall
CADD	5.317	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.05% South Asian · 8,239/91,042 alleles

Filtering AF 8.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.82%

Overall 2.76% 44,523/1,612,476 alleles · common exomes 38,934/1,460,586 · genomes 5,589/151,890 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	9.05%	11
Finnishnot grpmax-eligible	7.68%	13
Middle Eastern	6.66%	15
African / African-American	5.69%	18
Remaining individualsnot grpmax-eligible	2.82%	35
European (non-Finnish)	2.01%	50
Ashkenazi Jewishnot grpmax-eligible	1.71%	59
Admixed American	1.27%	79
East Asian	0.058%	1,725

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.Arg586=
Coding: c.1756C>A
MANE Select: NM_016156
dbSNP: rs61735577
Type: single nucleotide variant
Location: chr11:95836162 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4B1 Charcot-Marie-Tooth disease type 4

Similar variants

MTMR2 p.Arg586Gln Likely benign ★★ same residue
MTMR2 p.Arg586Gly Uncertain significance ★ ⚠ same residue
MTMR2 p.Arg586Trp Uncertain significance ★ ⚠ same residue
MTMR2 c.804+2T>G Likely pathogenic ★★ same condition
MTMR2 p.Arg102Ter Pathogenic/Likely pathogenic ★★ same condition
MTMR2 p.Arg162Ter Pathogenic ★★ same condition
MTMR2 p.Arg364Ter Pathogenic ★★ same condition
MTMR2 p.Gln590Ter Pathogenic ★★ 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-arg586 (accessed [today's date]).

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