RNF168 p.Ala128=
c.384G>A · rs372627713 · VCV1623947
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.044%, afr)
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 -0.91 | GERP -3.5, phastCons 0.002 |
| Overall | ||
| CADD | 9.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.044%
African / African-American · 33/75,026 alleles
Filtering AF
0.0321%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0281%
Overall
0.00248%
40/1,614,044 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.044% | 2,274 |
| East Asian | 0.00223% | 44,886 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
| South Asian | 0.0011% | 91,076 |
| European (non-Finnish) | 0.000339% | 294,990 |
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.Ala128=
- Coding
- c.384G>A
- MANE Select
- NM_152617
- dbSNP
- rs372627713
- Type
- single nucleotide variant
- Location
- chr3:196487573 (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 128
- an α-helix
Similar variants
- RNF168 p.Ala128Val Likely benign ★★ same residue
- RNF168 p.Ala128Thr 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
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-ala128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown