RBPJ p.Ser65=
c.195T>C · rs2270226 · VCV1164140
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 69.1%, amr) — too common for a highly-penetrant pathogenic allele
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 1.2 | GERP -0.39, phastCons 1 |
| Overall | ||
| CADD | 10.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
69.1%
Admixed American · 41,081/59,484 alleles
Filtering AF
68.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 68.3%
Overall
56.4%
907,732/1,609,306 alleles · common
exomes 829,245/1,458,958 · genomes 78,487/150,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 69.1% | 1 |
| Amishnot grpmax-eligible | 59.6% | 2 |
| Middle Eastern | 58.2% | 2 |
| Finnishnot grpmax-eligible | 57.3% | 2 |
| European (non-Finnish) | 57.1% | 2 |
| South Asian | 56.4% | 2 |
| Remaining individualsnot grpmax-eligible | 55.7% | 2 |
| East Asian | 55.6% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 52.7% | 2 |
| African / African-American | 37.1% | 3 |
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
- RBPJ
- Protein
- p.Ser65=
- Coding
- c.195T>C
- MANE Select
- NM_015874
- dbSNP
- rs2270226
- Type
- single nucleotide variant
- Location
- chr4:26415514 (GRCh38)
- Gene constraint
- LOEUF 0.267 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.76 · 4 PDB
- Residue 65
- the 'dna-binding' region
Similar variants
- RBPJ p.Ser65Asn Uncertain significance ★ ⚠ same residue
- RBPJ p.Arg17Gln Uncertain significance ★★ ⚠ same type
- RBPJ p.Arg181Ter Uncertain significance ★★ same type
- RBPJ p.Asp77Asn Uncertain significance ★★ ⚠ same type
- RBPJ p.Glu459Lys Uncertain significance ★★ ⚠ same type
- RBPJ p.Gly10Val Uncertain significance ★★ ⚠ same type
- RBPJ p.Pro86Leu Uncertain significance ★★ same type
- RBPJ p.Thr482Ile 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/rbpj-p-ser65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown