RB1 p.Glu672=
c.2016G>A · rs1555294098 · VCV458138
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
2
hereditary neoplastic syndrome
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 -0.44 | GERP -3.5, phastCons 0.045 |
| Overall | ||
| CADD | 4.941 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,906 alleles
Overall
6.2e-05%
1/1,613,832 alleles · very rare
exomes 1/1,461,750 · genomes 0/152,082 · joint denominator
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
- RB1
- Protein
- p.Glu672=
- Coding
- c.2016G>A
- MANE Select
- NM_000321
- dbSNP
- rs1555294098
- Type
- single nucleotide variant
- Location
- chr13:48459743 (GRCh38)
- Gene constraint
- LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.03 · 19 PDB
- Residue 672
- the 'pocket; binds t and e1a' region; the 'domain b' region
Similar variants
- RB1 p.Glu672Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
- RB1 p.Glu672fs Pathogenic ★ same residue
- RB1 p.Glu672Ter Pathogenic ★ same residue
- RB1 c.1049+1G>A Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.1049+1G>T Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.1049+3A>G Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.1050-2A>G Pathogenic/Likely pathogenic ★★ same condition
- RB1 c.1128-1G>A 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/rb1-p-glu672 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown