ERCC2 p.Phe568=
c.1704T>C · rs141944141 · VCV1656724
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0132%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.3 | GERP -3.3, phastCons 0.94 |
| Overall | ||
| CADD | 2.483 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0132%
South Asian · 12/91,066 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.00093%
15/1,613,638 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0132% | 7,589 |
| Admixed American | 0.00333% | 29,993 |
| African / African-American | 0.00133% | 74,940 |
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.Phe568=
- Coding
- c.1704T>C
- MANE Select
- NM_000400
- dbSNP
- rs141944141
- Type
- single nucleotide variant
- Location
- chr19:45353296 (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 568
- a β-strand; the 'mediates interaction with mms19' region
Similar variants
- ERCC2 p.Phe568Leu Uncertain significance ★ ⚠ same residue
- ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg616Pro Pathogenic ★★ same condition
- ERCC2 p.Phe568fs Pathogenic/Likely pathogenic ★★ same residue
- ERCC2 p.Ala108Thr Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala144Val Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala226Thr Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala306Val 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-phe568 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown