SETD5 p.Pro427fs
c.1278dup · VCV4961107
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
SETD5-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 haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 12 of 23 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.2 | GERP -0.67, phastCons 0.7 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SETD5
- Protein
- p.Pro427fs
- Coding
- c.1278dup
- MANE Select
- NM_001080517
- Type
- Duplication
- Location
- chr3:9445137 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
- Residue 427
- the 'disordered' region; a UniProt-annotated variant site (in mrd23)
Disease context
SETD5-related disorder
Similar variants
- SETD5 p.Thr805Ter Likely pathogenic ★ same condition
- SETD5 p.Pro427= Likely benign ★ same residue
- SETD5 p.Arg1174Ter Pathogenic/Likely pathogenic ★★ same condition
- SETD5 p.Arg445Ter Pathogenic ★★ same condition
- SETD5 p.Arg768Ter Pathogenic ★★ same condition
- SETD5 p.Gln1058Ter Pathogenic/Likely pathogenic ★★ same condition
- SETD5 p.Gln272Ter Pathogenic/Likely pathogenic ★★ same condition
- SETD5 p.Tyr391Cys 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/setd5-p-pro427fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown