MTM1 p.Cys113=
c.339T>C · rs147644722 · VCV285094
ClinGen expert panel — Congenital Myopathies VCEP
Benign for centronuclear myopathy. Applied ACMG criteria (verbatim):
BP7 BP4 BA1
Curation rationale (ClinGen, verbatim)
The variant NM_000252.3:c.339T>C in MTM1 is a synonymous (silent) variant (p.Cys113=). The highest population filtering allele frequency in gnomAD v4.1.0 is 0.003242 (198/54107 alleles, 58 hemizygotes) in African/African American population, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.000016) for BA1, and therefore meets this criterion (BA1). In addition, SpliceAI does not predict impact to splicing, and the variant occurs at a nucleotide that is not conserved as shown by UCSC Genome Browser (BP4, BP7). In summary, this variant meets the criteria to be classified as benign for X-linked centronuclear myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: BA1, BP4, BP7. (Congenital Myopathies VCEP specifications version 1; 8/7/2024)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 2.3 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 10.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.366% | 273 |
| Admixed American | 0.0553% | 1,808 |
| Remaining individualsnot grpmax-eligible | 0.0328% | 3,053 |
| European (non-Finnish) | 0.000659% | 151,796 |
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
- MTM1
- Protein
- p.Cys113=
- Coding
- c.339T>C
- MANE Select
- NM_000252
- dbSNP
- rs147644722
- Type
- single nucleotide variant
- Location
- chrX:150614696 (GRCh38)
- Structure
- AlphaFold pLDDT 90.10
Similar variants
- MTM1 p.Cys113Ter Pathogenic ★ same residue
- MTM1 c.1644+1G>A Pathogenic ★★★ same condition
- MTM1 p.Arg224Ter Pathogenic ★★★ same condition
- MTM1 p.Arg69Cys Pathogenic ★★★ same condition
- MTM1 p.Gln451= Likely pathogenic ★★★ same condition
- MTM1 p.Glu404Lys Pathogenic ★★★ same condition
- MTM1 p.Pro205Leu Pathogenic ★★★ same condition
- MTM1 p.Trp230Arg Likely pathogenic ★★★ 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/mtm1-p-cys113 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown