ERCC2 c.5+2T>A
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
cerebrooculofacioskeletal syndrome 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.96 | donor loss · deltas |
| Pangolin | Δ0.80 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 10 | GERP 1.8, phastCons 1 |
| Non-coding constraint | Z 1.16 | 1 kb window · o/e 0.92 · regional · uncalibrated |
| Overall | ||
| CADD | 29.9 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ERCC2
- Coding
- c.5+2T>A
- MANE Select
- NM_000400
- dbSNP
- rs1599753508
- Type
- single nucleotide variant
- Location
- chr19:45370534 (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 condition
- ERCC2 c.1308-2A>G Likely pathogenic ★★ same condition
- ERCC2 c.1378-1G>T Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 c.1479+2T>C Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 c.1480-1G>C Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 c.1480-2A>C Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 c.1544-1G>T Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 c.1666-1G>A Pathogenic/Likely pathogenic ★★ same condition
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-5-plus-2t-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown