Is MTMR2 p.Pro80= (c.240A>C) pathogenic?

MTMR2 p.Pro80= (c.240A>C) is classified Benign/Likely benign in MTMR2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-04). Rare (popmax 0.491%, sas); Associated with Inborn genetic diseases.

What condition is associated with MTMR2 p.Pro80= (c.240A>C)?

MTMR2 p.Pro80= (c.240A>C) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4B1, Charcot-Marie-Tooth disease (ClinVar).

How common is MTMR2 p.Pro80= (c.240A>C) in the general population?

MTMR2 p.Pro80= (c.240A>C) is rare (popmax 0.491%, sas) (gnomAD).

MTMR2 p.Pro80=

c.240A>C · rs201920176 · VCV414070

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.491%, sas)

Conditions

Inborn genetic diseases

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 -0.072	GERP -1.5, phastCons 0.89
Overall
CADD	9.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.491% South Asian · 447/91,080 alleles

Filtering AF 0.453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.438%

Overall 0.0291% 470/1,613,916 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.491%	204
Middle Eastern	0.0495%	2,020
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Admixed American	0.00333%	30,005
European (non-Finnish)	0.000424%	235,959

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.Pro80=
Coding: c.240A>C
MANE Select: NM_016156
dbSNP: rs201920176
Type: single nucleotide variant
Location: chr11:95865623 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 5 PDB
Residue 80: the gram domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

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.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-pro80 (accessed [today's date]).

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