GEN1 p.Ser509=
c.1527G>A · rs1465941666 · VCV1627496
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 0.43 | GERP -4, phastCons 0.065 |
| Overall | ||
| CADD | 5.102 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,002 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000248%
4/1,613,828 alleles · very rare
exomes 4/1,461,602 · genomes 0/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,001 |
| European (non-Finnish) | 0.00017% | 589,929 |
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.Ser509=
- Coding
- c.1527G>A
- MANE Select
- NM_001130009
- dbSNP
- rs1465941666
- Type
- single nucleotide variant
- Location
- chr2:17780739 (GRCh38)
- Gene constraint
- LOEUF 1.422 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
- Structure
- AlphaFold pLDDT 61.79 · 1 PDB
Similar variants
- GEN1 p.Ser509Trp Likely benign ★★ same residue
- GEN1 p.Ser509Leu 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
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-ser509 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown