ERCC4 p.Phe630=
c.1890T>C · rs1028415080 · VCV3061456
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00238%, nfe)
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 2.4 | GERP 0.37, phastCons 1 |
| Overall | ||
| CADD | 11.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00238%
European (non-Finnish) · 28/1,176,572 alleles
Filtering AF
0.00165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00142%
Overall
0.0018%
29/1,610,164 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00238% | 42,021 |
| African / African-American | 0.00134% | 74,846 |
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.Phe630=
- Coding
- c.1890T>C
- MANE Select
- NM_005236
- dbSNP
- rs1028415080
- Type
- single nucleotide variant
- Location
- chr16:13937844 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.60 · 13 PDB
Disease context
ERCC4-related disorder
Similar variants
- 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
- ERCC4 p.Ile546= Likely benign 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-phe630 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown