MYSM1 p.Ser758=
c.2274C>T · VCV4749182
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -0.39 | GERP -4.2 |
| Overall | ||
| CADD | 8.576 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,844 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000434%
7/1,612,172 alleles · very rare
exomes 6/1,460,104 · genomes 1/152,068 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,844 |
| South Asian | 0.0011% | 91,012 |
| European (non-Finnish) | 0.000424% | 235,725 |
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
- MYSM1
- Protein
- p.Ser758=
- Coding
- c.2274C>T
- MANE Select
- NM_001085487
- Type
- single nucleotide variant
- Location
- chr1:58661224 (GRCh38)
- Gene constraint
- LOEUF 0.578 · pLI 0.09 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.69 · 2 PDB
- Residue 758
- a UniProt-annotated variant site (in bmfs4)
Similar variants
- MYSM1 p.Arg506Ter Pathogenic ★★ same type
- MYSM1 p.Gln629Ter Pathogenic ★★ same type
- MYSM1 p.Arg138Gln Uncertain significance ★★ ⚠ same type
- MYSM1 p.Arg150Cys Uncertain significance ★★ ⚠ same type
- MYSM1 p.Arg204Cys Uncertain significance ★★ ⚠ same type
- MYSM1 p.Arg478Gln Uncertain significance ★★ ⚠ same type
- MYSM1 p.Arg494His Uncertain significance ★★ ⚠ same type
- MYSM1 p.Arg499His Uncertain significance ★★ ⚠ same type
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/mysm1-p-ser758 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown