GEN1 p.Asp306=
c.918T>C · VCV4844979
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.9 | GERP -4.2 |
| Overall | ||
| CADD | 0.269 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,178,320 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,610,652 alleles · very rare
exomes 2/1,458,552 · genomes 0/152,100 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- GEN1
- Protein
- p.Asp306=
- Coding
- c.918T>C
- MANE Select
- NM_001130009
- Type
- single nucleotide variant
- Location
- chr2:17772749 (GRCh38)
- Gene constraint
- LOEUF 1.422 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
- Structure
- AlphaFold pLDDT 61.79 · 1 PDB
- Residue 306
- the '5'-3' exonuclease domain' region
Similar variants
- GEN1 p.Asp306His Uncertain significance ★ ⚠ same residue
- GEN1 c.1264+1G>T Uncertain significance ★★ same type
- GEN1 c.953+4A>G Uncertain significance ★★ same type
- GEN1 p.Ala135Ser Uncertain significance ★★ ⚠ same type
- GEN1 p.Ala197Thr Uncertain significance ★★ ⚠ same type
- GEN1 p.Ala320Pro Uncertain significance ★★ ⚠ same type
- GEN1 p.Ala447Val Uncertain significance ★★ ⚠ same type
- GEN1 p.Ala448Thr Uncertain significance ★★ ⚠ 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/gen1-p-asp306 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown