Is MTMR2 p.Arg628= (c.1882A>C) pathogenic?

MTMR2 p.Arg628= (c.1882A>C) is classified Likely benign in MTMR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-24). Ultra-rare (popmax 0.0198%, sas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with MTMR2 p.Arg628= (c.1882A>C)?

MTMR2 p.Arg628= (c.1882A>C) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is MTMR2 p.Arg628= (c.1882A>C) in the general population?

MTMR2 p.Arg628= (c.1882A>C) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

MTMR2 p.Arg628=

c.1882A>C · rs777498850 · VCV2139187

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

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 0.21	GERP -4.9, phastCons 0.78
Overall
CADD	7.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% South Asian · 18/91,058 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00155% 25/1,613,138 alleles · ultra-rare exomes 25/1,460,932 · genomes 0/152,206 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,059
Remaining individualsnot grpmax-eligible	0.0048%	20,818
European (non-Finnish)	0.000339%	294,841

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.Arg628=
Coding: c.1882A>C
MANE Select: NM_016156
dbSNP: rs777498850
Type: single nucleotide variant
Location: chr11:95835340 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 5 PDB
Residue 628: the 'disordered' region

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.Arg628Ser 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
MTMR2 p.Ala397Gly 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-arg628 (accessed [today's date]).

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