SIM1 p.Arg728fs
c.2178_2187del · VCV3373643
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
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 | escapes | premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.4, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SIM1
- Protein
- p.Arg728fs
- Coding
- c.2178_2187del
- MANE Select
- NM_005068
- Type
- Deletion
- Location
- chr6:100390475 (GRCh38)
- Gene constraint
- LOEUF 0.332 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.70
- Residue 728
- the single-minded c-terminal domain
Similar variants
- SIM1 p.Gln206fs Pathogenic ★ same type
- SIM1 p.Gly214fs Pathogenic ★ same type
- SIM1 p.Met102_Tyr103insTer Pathogenic ★ same type
- SIM1 p.Gln206_Asn207delinsHis Uncertain significance ★ same type
- SIM1 p.Lys500fs Uncertain significance ★ same type
- SIM1 c.175+93_175+97del Benign ★ same type
- SIM1 c.544-14del Likely benign ★ same type
- SIM1 p.Ala212_Val213del 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/sim1-p-arg728fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown