ERCC6 p.Ala295=
c.885T>C · rs4253044 · VCV1108270
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.052%, 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 0.45 | GERP -2.8, phastCons 0.45 |
| Overall | ||
| CADD | 8.026 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.052%
African / African-American · 39/75,022 alleles
Filtering AF
0.039%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0345%
Overall
0.00285%
46/1,614,138 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.052% | 1,924 |
| Admixed American | 0.00666% | 15,005 |
| East Asian | 0.00446% | 22,443 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,508 |
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.Ala295=
- Coding
- c.885T>C
- MANE Select
- NM_000124
- dbSNP
- rs4253044
- Type
- single nucleotide variant
- Location
- chr10:49524545 (GRCh38)
- Gene constraint
- LOEUF 0.803 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.12 · 12 PDB
- Residue 295
- the 'disordered' region; the 'n-terminal domain; essential for its chromatin remodeling activity' region
Similar variants
- ERCC6 p.Ala295Thr Uncertain significance ★ ⚠ same residue
- ERCC6 p.Ala295Val Uncertain significance ★ ⚠ same residue
- PGBD3 p.Tyr295Cys Uncertain significance ★ ⚠ 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-ala295 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown