SETD5 p.Ser677fs
c.2028del · VCV4961116
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 15 of 23 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -3.4, phastCons 0.99 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SETD5
- Protein
- p.Ser677fs
- Coding
- c.2028del
- MANE Select
- NM_001080517
- Type
- Deletion
- Location
- chr3:9447929 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
- Residue 677
- the 'disordered' region; a UniProt-annotated variant site (in mrd23)
Disease context
SETD5-related disorder
Similar variants
- SETD5 p.Ser677Cys Uncertain significance ★ ⚠ same residue
- SETD5 p.Ala918fs Likely pathogenic ★ same condition
- SETD5 p.Leu1068fs Likely pathogenic ★ same condition
- SETD5 p.Leu771fs Likely pathogenic ★ same condition
- SETD5 p.Pro1054fs Likely pathogenic ★ same condition
- SETD5 p.Ser962fs Likely pathogenic ★ same condition
- SETD5 p.Val305fs Pathogenic ★ same condition
- SETD5 p.Glu661fs 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-ser677fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown