ERCC8 p.Gln380=
c.1140A>G · rs138752036 · VCV736240
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0561%, afr)
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 -3.1 | GERP -3.8 |
| Overall | ||
| CADD | 3.481 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0561%
African / African-American · 42/74,846 alleles
Filtering AF
0.0426%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0379%
Overall
0.00639%
103/1,610,892 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0561% | 1,782 |
| Middle Eastern | 0.0335% | 2,986 |
| South Asian | 0.0101% | 9,949 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,803 |
| European (non-Finnish) | 0.00399% | 25,091 |
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.Gln380=
- Coding
- c.1140A>G
- MANE Select
- NM_000082
- dbSNP
- rs138752036
- Type
- single nucleotide variant
- Location
- chr5:60874666 (GRCh38)
- Gene constraint
- LOEUF 1.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.72 · 16 PDB
- Residue 380
- a UniProt-annotated variant site (in csa); the 'disordered' region
Similar variants
- ERCC8 p.Gln380fs Uncertain significance same residue
- ERCC8 c.1041+1G>T Pathogenic/Likely pathogenic ★★ same type
- ERCC8 c.1042-2A>G Pathogenic/Likely pathogenic ★★ same type
- ERCC8 c.173+1119G>C Pathogenic/Likely pathogenic ★★ same type
- ERCC8 c.173+1G>A Pathogenic/Likely pathogenic ★★ same type
- ERCC8 c.275+1G>A Pathogenic ★★ same type
- ERCC8 c.276-1G>A Likely pathogenic ★★ same type
- ERCC8 c.399+1G>A Likely pathogenic ★★ 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/ercc8-p-gln380 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown