DEF6 p.Lys74fs
c.220_227del · VCV3646878
Pathogenic
Single submitter
Classification
Pathogenic
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 |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 11 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 0.92, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- DEF6
- Protein
- p.Lys74fs
- Coding
- c.220_227del
- MANE Select
- NM_022047
- Type
- Deletion
- Location
- chr6:35309793 (GRCh38)
- Gene constraint
- LOEUF 0.61 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.91
Similar variants
- DEF6 p.Lys74Ter Pathogenic ★ same residue
- DEF6 p.Leu159fs Likely pathogenic ★ same type
- DEF6 p.Leu179fs Pathogenic ★ same type
- DEF6 p.Leu271fs Pathogenic ★ same type
- DEF6 c.1383-11_1383-8del Uncertain significance ★ same type
- DEF6 p.Glu169_Gln171del Uncertain significance ★ same type
- DEF6 c.237+14del Likely benign ★ 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/def6-p-lys74fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown