MTMR2 p.Ile138=
c.414T>C · rs754358489 · VCV1113630
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
1
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 1.8 | GERP -4.5, phastCons 1 |
| Overall | ||
| CADD | 7.838 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,996 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.00031%
5/1,613,842 alleles · very rare
exomes 4/1,461,638 · genomes 1/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,998 |
| European (non-Finnish) | 0.000254% | 393,306 |
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.Ile138=
- Coding
- c.414T>C
- MANE Select
- NM_016156
- dbSNP
- rs754358489
- Type
- single nucleotide variant
- Location
- chr11:95862046 (GRCh38)
- Gene constraint
- LOEUF 0.9 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.44 · 5 PDB
- Residue 138
- the gram domain; a β-strand
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-ile138 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown