ERCC6 p.Arg652=
c.1954C>A · rs767247987 · VCV2897119
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.28 | donor gain, 44 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.33 | gain · loss 0.04 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 0.76, phastCons 1 |
| Overall | ||
| CADD | 15.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,078 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.000434%
7/1,614,098 alleles · very rare
exomes 7/1,461,830 · genomes 0/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,180 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
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.Arg652=
- Coding
- c.1954C>A
- MANE Select
- NM_000124
- dbSNP
- rs767247987
- Type
- single nucleotide variant
- Location
- chr10:49483384 (GRCh38)
- Gene constraint
- LOEUF 0.803 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.12 · 12 PDB
- Residue 652
- the helicase atp-binding domain; a UniProt-annotated variant site (in a colorectal cancer sample; somatic mutation)
Similar variants
- ERCC6 p.Arg652Ter Pathogenic/Likely pathogenic ★★ same residue
- ERCC6 p.Arg652Gln Uncertain significance ★ ⚠ same residue
- ERCC6 p.Arg652fs Pathogenic ★ 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
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-arg652 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown