GEN1 p.Ala83=
c.249T>A · rs373047766 · VCV1142737
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
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 -0.072 | GERP -2.8, phastCons 0.87 |
| Overall | ||
| CADD | 9.283 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,858 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.000744%
12/1,613,314 alleles · ultra-rare
exomes 11/1,460,984 · genomes 1/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,476 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,615 |
| European (non-Finnish) | 0.00017% | 589,644 |
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.Ala83=
- Coding
- c.249T>A
- MANE Select
- NM_001130009
- dbSNP
- rs373047766
- Type
- single nucleotide variant
- Location
- chr2:17761483 (GRCh38)
- Gene constraint
- LOEUF 1.422 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
- Structure
- AlphaFold pLDDT 61.79 · 1 PDB
- Residue 83
- the 'xpg-n domain' region
Similar variants
- 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
- GEN1 p.Ala454Thr 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-ala83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown