ERCC8 p.Ala21=
c.63A>G · rs754931194 · VCV1078001
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00892%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.41 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -3.8 |
| Overall | ||
| CADD | 10.45 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00892%
East Asian · 4/44,864 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.000479%
7/1,461,600 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00892% | 11,216 |
| Admixed American | 0.00167% | 60,024 |
| South Asian | 0.0011% | 91,072 |
| European (non-Finnish) | 8.48e-05% | 1,179,752 |
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.Ala21=
- Coding
- c.63A>G
- MANE Select
- NM_000082
- dbSNP
- rs754931194
- Type
- single nucleotide variant
- Location
- chr5:60944946 (GRCh38)
- Gene constraint
- LOEUF 1.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.72 · 16 PDB
- Residue 21
- an α-helix
Similar variants
- 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
- ERCC8 c.551-1G>A 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-ala21 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown