RNF168 p.Pro275=
c.825G>A · rs539422622 · VCV748887
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 · C>A here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.44 | GERP -2.1, phastCons 1 |
| Overall | ||
| CADD | 11.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,884 alleles
Filtering AF
0.000248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000498%
8/1,607,458 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,884 |
| European (non-Finnish) | 0.000596% | 167,759 |
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
- RNF168
- Protein
- p.Pro275=
- Coding
- c.825G>A
- MANE Select
- NM_152617
- dbSNP
- rs539422622
- Type
- single nucleotide variant
- Location
- chr3:196472710 (GRCh38)
- Gene constraint
- LOEUF 1.406 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.97 · 39 PDB
- Residue 275
- the 'disordered' region
Similar variants
- RNF168 p.Pro275Leu Uncertain significance ★★ ⚠ same residue
- RNF168 p.Arg131Ter Pathogenic/Likely pathogenic ★★ same type
- RNF168 p.Arg165Ter Pathogenic/Likely pathogenic ★★ same type
- RNF168 p.Glu138Ter Pathogenic/Likely pathogenic ★★ same type
- RNF168 p.Ala141Val Uncertain significance ★★ ⚠ same type
- RNF168 p.Ala7Ser Uncertain significance ★★ ⚠ same type
- RNF168 p.Arg131Gln Uncertain significance ★★ ⚠ same type
- RNF168 p.Arg132Trp Uncertain significance ★★ ⚠ 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/rnf168-p-pro275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown