ERCC4 p.Pro526=
c.1578G>A · rs757281318 · VCV3031863
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Conditions
1
ERCC4-related disorder
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 -4.2 | GERP -3.1 |
| Overall | ||
| CADD | 0.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,008 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000342%
5/1,461,850 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,003 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 8.47e-05% | 1,179,998 |
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
- ERCC4
- Protein
- p.Pro526=
- Coding
- c.1578G>A
- MANE Select
- NM_005236
- dbSNP
- rs757281318
- Type
- single nucleotide variant
- Location
- chr16:13935510 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.60 · 13 PDB
- Residue 526
- the 'disordered' region
Disease context
ERCC4-related disorder
Similar variants
- ERCC4 p.Pro526Leu Uncertain significance ★★ ⚠ same residue
- ERCC4 c.793-2A>G Pathogenic ★★ same condition
- ERCC4 p.Arg20Ter Pathogenic ★★ same condition
- ERCC4 p.Arg589Trp Pathogenic/Likely pathogenic ★★ same condition
- ERCC4 p.Gln296Ter Pathogenic/Likely pathogenic ★★ same condition
- ERCC4 p.Arg292Ter Likely pathogenic ★ same condition
- ERCC4 p.Cys236Ter Likely pathogenic ★ same condition
- ERCC4 p.Asp650Asn Uncertain significance ⚠ same condition
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/ercc4-p-pro526 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown