ERCC6 p.Ser708=
c.2124C>T · rs114832108 · VCV284589
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.298%, 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 -9.5 | GERP -3.8 |
| Overall | ||
| CADD | 0.302 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.298%
African / African-American · 223/74,878 alleles
Filtering AF
0.266%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.253%
Overall
0.0187%
301/1,613,774 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.298% | 336 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,682 |
| Admixed American | 0.0133% | 7,499 |
| European (non-Finnish) | 0.005% | 19,999 |
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.Ser708=
- Coding
- c.2124C>T
- MANE Select
- NM_000124
- dbSNP
- rs114832108
- Type
- single nucleotide variant
- Location
- chr10:49482732 (GRCh38)
- Gene constraint
- LOEUF 0.803 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.12 · 12 PDB
- Residue 708
- an α-helix
Similar variants
- 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
- ERCC6 c.2709+1G>T 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-ser708 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown