SPRED1 p.Ile245fs
c.733del · VCV4811480
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Legius syndrome
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 haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -0.68, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SPRED1
- Protein
- p.Ile245fs
- Coding
- c.733del
- MANE Select
- NM_152594
- Type
- Deletion
- Location
- chr15:38351062 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.98 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.67 · 3 PDB
- Residue 245
- the kbd domain
Similar variants
- SPRED1 p.Ile245Thr Uncertain significance ★★ ⚠ same residue
- SPRED1 p.Gly350fs Pathogenic/Likely pathogenic ★★ same condition
- SPRED1 p.Lys289fs Pathogenic/Likely pathogenic ★★ same condition
- SPRED1 p.Met266fs Pathogenic/Likely pathogenic ★★ same condition
- SPRED1 p.Ser176del Uncertain significance ★★ same condition
- SPRED1 c.423+1del Likely pathogenic ★ same condition
- SPRED1 p.Ala409fs Pathogenic ★ same condition
- SPRED1 p.Arg110fs 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/spred1-p-ile245fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown