SIM1 p.Lys500fs
c.1499del · VCV4293496
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
SIM1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 11 of 12 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 1.2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SIM1
- Protein
- p.Lys500fs
- Coding
- c.1499del
- MANE Select
- NM_005068
- Type
- Deletion
- Location
- chr6:100393558 (GRCh38)
- Gene constraint
- LOEUF 0.332 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.70
- Residue 500
- the single-minded c-terminal domain
Disease context
SIM1-related disorder
Similar variants
- SIM1 p.Ala212_Val213del Uncertain significance same condition
- SIM1 c.1571-3del Likely benign same condition
- SIM1 p.Arg374Trp Uncertain significance ★★ ⚠ same condition
- SIM1 p.Ser199Cys Uncertain significance ★★ same condition
- SIM1 p.Gly480Ter Likely pathogenic ★ same condition
- SIM1 p.Leu265fs Likely pathogenic ★ same condition
- SIM1 p.Phe56fs Likely pathogenic ★ same condition
- SIM1 p.Thr481fs 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/sim1-p-lys500fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown