Is MTMR2 p.Ala54= (c.162C>T) pathogenic?

MTMR2 p.Ala54= (c.162C>T) is classified Uncertain significance in MTMR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0132%, sas); Associated with Charcot-Marie-Tooth disease type 4B1.

What condition is associated with MTMR2 p.Ala54= (c.162C>T)?

MTMR2 p.Ala54= (c.162C>T) is associated with Charcot-Marie-Tooth disease type 4B1 (ClinVar).

How common is MTMR2 p.Ala54= (c.162C>T) in the general population?

MTMR2 p.Ala54= (c.162C>T) is ultra-rare (popmax 0.0132%, sas) (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.Ala54=

c.162C>T · rs547213836 · VCV881266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Conditions

Charcot-Marie-Tooth disease type 4B1

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 0.13	GERP -2.2, phastCons 0.99
Overall
CADD	10.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 12/91,020 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00143% 23/1,612,820 alleles · ultra-rare exomes 21/1,460,670 · genomes 2/152,150 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,585
African / African-American	0.004%	24,980
Remaining individualsnot grpmax-eligible	0.0016%	62,458
European (non-Finnish)	0.000594%	168,458

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.Ala54=
Coding: c.162C>T
MANE Select: NM_016156
dbSNP: rs547213836
Type: single nucleotide variant
Location: chr11:95888180 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 5 PDB
Residue 54: the 'disordered' region

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

For Charcot-Marie-Tooth disease type 4B1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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
MTMR2 p.Glu574Ter Pathogenic/Likely pathogenic ★★ same condition
MTMR2 c.-222G>C Uncertain significance ★★ same condition
MTMR2 c.*212A>C 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-ala54 (accessed [today's date]).

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