GEN1 p.Cys321=
c.963C>T · rs1270602185 · VCV1146564
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000783%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 9.839 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000783%
European (non-Finnish) · 9/1,149,838 alleles
Filtering AF
0.000368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000267%
Overall
0.000571%
9/1,576,912 alleles · very rare
exomes 9/1,425,054 · genomes 0/151,858 · 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.Cys321=
- Coding
- c.963C>T
- MANE Select
- NM_001130009
- dbSNP
- rs1270602185
- Type
- single nucleotide variant
- Location
- chr2:17773105 (GRCh38)
- Gene constraint
- LOEUF 1.422 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
- Structure
- AlphaFold pLDDT 61.79 · 1 PDB
- Residue 321
- the '5'-3' exonuclease domain' region; an α-helix
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-cys321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown