RNF168 p.Ser111=
c.333T>C · rs764386439 · VCV1592148
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0171%, nfe)
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 3.8 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 9.615 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0171%
European (non-Finnish) · 201/1,175,856 alleles
Filtering AF
0.0152%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0143%
Overall
0.0132%
212/1,609,148 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0171% | 5,850 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,788 |
| Admixed American | 0.005% | 19,986 |
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.Ser111=
- Coding
- c.333T>C
- MANE Select
- NM_152617
- dbSNP
- rs764386439
- Type
- single nucleotide variant
- Location
- chr3:196488652 (GRCh38)
- Gene constraint
- LOEUF 1.406 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.97 · 39 PDB
Similar variants
- RNF168 p.Ser111Cys 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-ser111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown