ERCC2 p.Tyr339=
c.1017C>T · rs1412068236 · VCV1747538
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00763%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.28 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.8 | GERP -3.6 |
| Overall | ||
| CADD | 1.555 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00763%
European (non-Finnish) · 88/1,153,954 alleles
Filtering AF
0.00628%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00586%
Overall
0.00601%
93/1,548,648 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00763% | 13,113 |
| Remaining individualsnot grpmax-eligible | 0.00497% | 20,129 |
| African / African-American | 0.00272% | 36,732 |
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
- Protein
- p.Tyr339=
- Coding
- c.1017C>T
- MANE Select
- NM_000400
- dbSNP
- rs1412068236
- Type
- single nucleotide variant
- Location
- chr19:45363844 (GRCh38)
- Gene constraint
- LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.74 · 55 PDB
- Residue 339
- an α-helix
Similar variants
- ERCC2 p.Tyr339Asn Uncertain significance ★ ⚠ same residue
- ERCC2 p.Tyr339Ter Pathogenic/Likely pathogenic ★★ same residue
- MAG p.Glu339Asp Uncertain significance ★★ ⚠ same residue
- ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg616Pro Pathogenic ★★ same condition
- ERCC2 p.Ala108Thr Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala144Val Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala226Thr Uncertain significance ★★ ⚠ 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-p-tyr339 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown