GEN1 p.Phe159fs
c.472_475dup · VCV3893115
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
GEN1-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 |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 14 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- GEN1
- Protein
- p.Phe159fs
- Coding
- c.472_475dup
- MANE Select
- NM_001130009
- Type
- Duplication
- Location
- chr2:17765018 (GRCh38)
- Gene constraint
- LOEUF 1.422 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
- Structure
- AlphaFold pLDDT 61.79 · 1 PDB
- Residue 159
- the 'xpg-i domain' region; a turn
Disease context
GEN1-related disorder
Similar variants
- GEN1 p.Phe159Cys Uncertain significance ★ ⚠ same residue
- GEN1 p.Phe159Leu Uncertain significance ★ ⚠ same residue
- GEN1 p.Phe159Ser Uncertain significance ★ ⚠ same residue
- GEN1 p.His178Asn Uncertain significance ★★ ⚠ same condition
- GEN1 p.Pro250Leu Uncertain significance ★★ ⚠ same condition
- GEN1 p.Thr105Arg Uncertain significance ★★ ⚠ same condition
- GEN1 p.Arg898Cys Benign/Likely benign ★★ same condition
- GEN1 p.Lys882Glu Benign ★★ 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/gen1-p-phe159fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown