Is MTMR2 p.Pro478= (c.1434T>G) pathogenic?

MTMR2 p.Pro478= (c.1434T>G) is classified Likely benign in MTMR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-04). Very rare (popmax 0.00133%, afr); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with MTMR2 p.Pro478= (c.1434T>G)?

MTMR2 p.Pro478= (c.1434T>G) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is MTMR2 p.Pro478= (c.1434T>G) in the general population?

MTMR2 p.Pro478= (c.1434T>G) is very rare (popmax 0.00133%, afr) (gnomAD).

MTMR2 p.Pro478=

c.1434T>G · rs2135417185 · VCV1619120

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, 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 0.71	GERP -5.3, phastCons 0.95
Overall
CADD	8.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,050 alleles

Overall 6.2e-05% 1/1,613,938 alleles · very rare exomes 1/1,461,610 · genomes 0/152,328 · 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.Pro478=
Coding: c.1434T>G
MANE Select: NM_016156
dbSNP: rs2135417185
Type: single nucleotide variant
Location: chr11:95841662 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 5 PDB
Residue 478: the myotubularin phosphatase domain

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 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
MTMR2 p.Ala497Thr 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-pro478 (accessed [today's date]).

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