ERCC2 c.1237+3A>G
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00268%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +3 | donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -3.6 |
| Non-coding constraint | Z 1.55 | 1 kb window · o/e 0.87 · regional · uncalibrated |
| Overall | ||
| CADD | 8.871 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00268%
African / African-American · 2/74,712 alleles
Filtering AF
0.000444%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000187%
3/1,603,816 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00268% | 37,356 |
| Admixed American | 0.00167% | 59,976 |
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+3A>G
- MANE Select
- NM_000400
- dbSNP
- rs1440327008
- Type
- single nucleotide variant
- Location
- chr19:45361521 (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-3a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown