ERCC2 p.Phe233=
c.699C>T · rs141816180 · VCV736815
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.806%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -3.5 |
| Overall | ||
| CADD | 3.423 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.806%
African / African-American · 605/75,036 alleles
Filtering AF
0.753%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.732%
Overall
0.047%
758/1,613,944 alleles · rare
exomes 419/1,461,674 · genomes 339/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.806% | 124 |
| Admixed American | 0.0916% | 1,091 |
| Remaining individualsnot grpmax-eligible | 0.0656% | 1,524 |
| Middle Eastern | 0.0331% | 3,025 |
| European (non-Finnish) | 0.00441% | 22,692 |
| South Asian | 0.00329% | 30,361 |
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.Phe233=
- Coding
- c.699C>T
- MANE Select
- NM_000400
- dbSNP
- rs141816180
- Type
- single nucleotide variant
- Location
- chr19:45364443 (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 233
- the helicase atp-binding domain; a β-strand
Similar variants
- MAG p.Ser233Arg Uncertain significance ★ same residue
- ERCC2 c.816-2A>G Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Ala717Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg511Gln Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg601Leu Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg616Pro Pathogenic ★★ same condition
- ERCC2 p.Arg616Trp 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-p-phe233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown