Is MTMR2 p.Asp90Val (c.269A>T) pathogenic?

MTMR2 p.Asp90Val (c.269A>T) is classified Uncertain significance in MTMR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-07). AlphaMissense: likely pathogenic (0.9341); Very rare (popmax 0.00223%, eas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with MTMR2 p.Asp90Val (c.269A>T)?

MTMR2 p.Asp90Val (c.269A>T) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is MTMR2 p.Asp90Val (c.269A>T) in the general population?

MTMR2 p.Asp90Val (c.269A>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MTMR2 p.Asp90Val (c.269A>T)?

AlphaMissense predicts likely pathogenic (score 0.9341) — an in-silico prediction, not a clinical call.

MTMR2 p.Asp90Val

c.269A>T · rs147341114 · VCV1047274

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9341 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
AlphaMissense	0.9341	likely pathogenic
REVEL	0.914	moderately pathogenic-leaning
SaProt	LLR -10.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 47 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,854 alleles

Overall 0.000186% 3/1,613,770 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,854
African / African-American	0.00133%	75,058
European (non-Finnish)	8.48e-05%	1,179,711

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.Asp90Val
Coding: c.269A>T
MANE Select: NM_016156
dbSNP: rs147341114
Type: single nucleotide variant
Location: chr11:95862360 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 5 PDB
Residue 90: the gram domain; a β-strand

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-asp90val (accessed [today's date]).

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