Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.27%, mid)
Conditions
1
Cockayne syndrome type 1
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 1.9 | GERP -0.11, phastCons 1 |
| Overall | ||
| CADD | 15.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.27%
Middle Eastern · 197/6,030 alleles
Filtering AF
2.89%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.75%
Overall
1.85%
29,648/1,598,376 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 3.27% | 31 |
| European (non-Finnish) | 2.15% | 47 |
| South Asian | 1.92% | 52 |
| Remaining individualsnot grpmax-eligible | 1.87% | 54 |
| Admixed American | 1.12% | 89 |
| Ashkenazi Jewishnot grpmax-eligible | 1.07% | 93 |
| Finnishnot grpmax-eligible | 0.415% | 241 |
| African / African-American | 0.356% | 281 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| East Asian | 0.00447% | 22,387 |
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.Asp121=
- Coding
- c.363T>C
- MANE Select
- NM_000082
- dbSNP
- rs4647088
- Type
- single nucleotide variant
- Location
- chr5:60918301 (GRCh38)
- Gene constraint
- LOEUF 1.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.72 · 16 PDB
- Residue 121
- a turn
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 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
- ERCC8 c.399+1G>A Likely pathogenic ★★ same condition
- ERCC8 c.551-1G>A 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-asp121 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown