ERCC8 p.Glu22=
c.66G>A · rs149130938 · VCV354023
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.028 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 11.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.29% | 344 |
| Middle Easterngrpmax | 0.231% | 433 |
| Remaining individualsnot grpmax-eligible | 0.152% | 658 |
| European (non-Finnish) | 0.137% | 730 |
| Admixed American | 0.115% | 870 |
| South Asian | 0.09% | 1,111 |
| African / African-American | 0.028% | 3,573 |
| Finnishnot grpmax-eligible | 0.0156% | 6,403 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- ERCC8
- Protein
- p.Glu22=
- Coding
- c.66G>A
- MANE Select
- NM_000082
- dbSNP
- rs149130938
- Type
- single nucleotide variant
- Location
- chr5:60944943 (GRCh38)
- Gene constraint
- LOEUF 1.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.72 · 16 PDB
- Residue 22
- an α-helix
Disease context
Cockayne syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Cockayne syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- ERCC8 p.Glu22Asp Uncertain significance ★ ⚠ same residue
- ERCC8 p.Glu22Lys Uncertain significance ★ ⚠ same residue
- ERCC8 c.1041+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ERCC8 c.1042-2A>G Pathogenic/Likely pathogenic ★★ same condition
- ERCC8 c.173+1119G>C Pathogenic/Likely pathogenic ★★ same condition
- ERCC8 c.173+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ERCC8 c.275+1G>A Pathogenic ★★ same condition
- ERCC8 c.276-1G>A 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/ercc8-p-glu22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown