Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.1%, afr)
Conditions
3
age related macular degeneration 5
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 0.11 | GERP -0.49, phastCons 0.96 |
| Overall | ||
| CADD | 3.274 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.1%
African / African-American · 1,579/75,030 alleles
Filtering AF
2.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.98%
Overall
0.147%
2,374/1,613,994 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.1% | 48 |
| Middle Eastern | 1.07% | 93 |
| Remaining individualsnot grpmax-eligible | 0.256% | 391 |
| Admixed American | 0.168% | 594 |
| Ashkenazi Jewishnot grpmax-eligible | 0.142% | 705 |
| South Asian | 0.0384% | 2,602 |
| European (non-Finnish) | 0.0331% | 3,018 |
| East Asian | 0.00223% | 44,870 |
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
- ERCC6
- Protein
- p.Glu382=
- Coding
- c.1146G>A
- MANE Select
- NM_000124
- dbSNP
- rs4253045
- Type
- single nucleotide variant
- Location
- chr10:49524284 (GRCh38)
- Gene constraint
- LOEUF 0.803 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.12 · 12 PDB
- Residue 382
- the 'disordered' region; the 'n-terminal domain; essential for its chromatin remodeling activity' region
Similar variants
- ERCC6 p.Glu382_Glu384del Uncertain significance ★ same residue
- ERCC6 p.Glu382_Glu384dup Uncertain significance same residue
- ERCC6 p.Glu382Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- ERCC6 c.1397+1G>C Likely pathogenic ★★ same condition
- ERCC6 c.1526+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ERCC6 c.2169+1G>A Likely pathogenic ★★ same condition
- ERCC6 c.2170-1G>A Pathogenic/Likely pathogenic ★★ same condition
- ERCC6 c.2286+1G>A Pathogenic/Likely pathogenic ★★ 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/ercc6-p-glu382 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown