ERCC4 p.Ile706=
c.2118T>C · rs777766206 · VCV726488
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
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 -3.5 | GERP -2.1 |
| Overall | ||
| CADD | 1.502 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/60,014 alleles
Filtering AF
0.00661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.00279%
45/1,614,118 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,502 |
| European (non-Finnish) | 0.00305% | 32,779 |
| South Asian | 0.0011% | 91,084 |
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.Ile706=
- Coding
- c.2118T>C
- MANE Select
- NM_005236
- dbSNP
- rs777766206
- Type
- single nucleotide variant
- Location
- chr16:13947714 (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 706
- the ercc4 domain; a UniProt-annotated variant site (in); the 'nuclease' region
Similar variants
- ERCC4 p.Ile706Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- ERCC4 c.1102+1G>T Likely pathogenic ★★ same type
- ERCC4 c.793-2A>G Pathogenic ★★ same type
- ERCC4 p.Arg20Ter Pathogenic ★★ same type
- ERCC4 p.Arg589Trp Pathogenic/Likely pathogenic ★★ same type
- ERCC4 p.Arg689Ser Likely pathogenic ★★ same type
- ERCC4 p.Arg772Ter Pathogenic/Likely pathogenic ★★ same type
- ERCC4 p.Cys236Arg 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/ercc4-p-ile706 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown