ERCC3 p.Phe297Ser
c.890T>C · rs145267069 · VCV1520987
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9992 | likely pathogenic · top 5% in ERCC3 |
|---|---|---|
| REVEL | 0.821 | moderately pathogenic-leaning |
| SaProt | LLR -15.86 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.84 | unconstrained · MANE · 36 kb · p 4.8e-07 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0266% | 3,766 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| European (non-Finnish)grpmax | 0.000509% | 196,653 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Phe297Ser
- Coding
- c.890T>C
- MANE Select
- NM_000122
- dbSNP
- rs145267069
- Type
- single nucleotide variant
- Location
- chr2:127288797 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.34 · 56 PDB
- Residue 297
- an α-helix
Similar variants
- ERCC3 p.Phe297Cys Uncertain significance ★ ⚠ same residue
- ERCC3 p.Phe297= Likely benign ★ same residue
- 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
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-phe297ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown