ERCC2 c.1237+293C>T
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.95%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +293 | deep intronic (+293 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.9 | GERP -1.7 |
| Non-coding constraint | Z 1.55 | 1 kb window · o/e 0.87 · regional · uncalibrated |
| Overall | ||
| CADD | 0.351 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.95%
African / African-American · 2,453/41,250 alleles
Filtering AF
5.75%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.67%
Overall
1.71%
2,591/151,504 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.95% | 17 |
| Remaining individualsnot grpmax-eligible | 1.34% | 75 |
| Admixed American | 0.598% | 167 |
| Middle Eastern | 0.345% | 290 |
| South Asian | 0.0626% | 1,597 |
| European (non-Finnish) | 0.0221% | 4,529 |
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
- ERCC2
- Coding
- c.1237+293C>T
- MANE Select
- NM_000400
- dbSNP
- rs3916825
- Type
- single nucleotide variant
- Location
- chr19:45361231 (GRCh38)
- Gene constraint
- LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.74 · 55 PDB
Similar variants
- ERCC2 c.1238-1G>C Likely pathogenic ★★ same type
- ERCC2 c.1308-2A>G Likely pathogenic ★★ same type
- ERCC2 c.1378-1G>T Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1479+2T>C Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1480-1G>C Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1480-2A>C Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1544-1G>T Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1666-1G>A 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/ercc2-c-1237-plus-293c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown