ERCC6 p.Pro591=
c.1773C>T · VCV3778025
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
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 -1.1 | GERP -0.64 |
| Overall | ||
| CADD | 2.312 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,886 alleles
Filtering AF
0.000878%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000717%
Overall
0.00149%
24/1,614,002 alleles · very rare
exomes 20/1,461,872 · genomes 4/152,130 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,443 |
| South Asian | 0.00329% | 30,362 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,240 |
| European (non-Finnish) | 0.00144% | 69,413 |
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.Pro591=
- Coding
- c.1773C>T
- MANE Select
- NM_000124 · reported on NM_001277058
- Type
- single nucleotide variant
- Location
- chr10:49516746 (GRCh38)
- Gene constraint
- LOEUF 0.803 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.12 · 12 PDB
- Residue 591
- the helicase atp-binding domain; a UniProt-annotated variant site (in a colorectal cancer sample; somatic mutation)
Similar variants
- ERCC6 p.Pro591Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- ERCC6 c.1397+1G>C Likely pathogenic ★★ same type
- ERCC6 c.1526+1G>T Pathogenic/Likely pathogenic ★★ same type
- ERCC6 c.2169+1G>A Likely pathogenic ★★ same type
- ERCC6 c.2170-1G>A Pathogenic/Likely pathogenic ★★ same type
- ERCC6 c.2286+1G>A Pathogenic/Likely pathogenic ★★ same type
- ERCC6 c.2287-2A>G Pathogenic/Likely pathogenic ★★ same type
- ERCC6 c.2599-26A>G Pathogenic/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/ercc6-p-pro591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown