ERCC3 p.Phe176=
c.528C>T · VCV4747748
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0417%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.106 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.22 | acceptor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP -7 | GERP -5 |
| Overall | ||
| CADD | 4.709 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0417%
South Asian · 38/91,060 alleles
Filtering AF
0.0312%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0276%
Overall
0.00335%
54/1,614,124 alleles · ultra-rare
exomes 51/1,461,864 · genomes 3/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0417% | 2,396 |
| East Asian | 0.00223% | 44,880 |
| Admixed American | 0.00167% | 60,024 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 0.0011% | 90,770 |
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
- ERCC3
- Protein
- p.Phe176=
- Coding
- c.528C>T
- MANE Select
- NM_000122
- Type
- single nucleotide variant
- Location
- chr2:127289818 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.34 · 56 PDB
- Residue 176
- a β-strand
Similar variants
- ERCC3 c.1828-1G>C Likely pathogenic ★★ same type
- ERCC3 c.471+1G>A Pathogenic ★★ same type
- ERCC3 c.657+1G>A Likely pathogenic ★★ same type
- ERCC3 p.Arg109Ter Pathogenic/Likely pathogenic ★★ same type
- ERCC3 p.Arg195Ter Pathogenic ★★ same type
- ERCC3 p.Arg234Ter Pathogenic/Likely pathogenic ★★ same type
- ERCC3 p.Arg425Ter Pathogenic ★★ same type
- ERCC3 p.Arg452Ter 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/ercc3-p-phe176 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown