ESRRB p.Arg312Cys
c.934C>T · rs1276962033 · VCV1695704
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0181%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.617 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 2.3, phastCons 1 |
| Regional constraint | o/e 0.80 | unconstrained · MANE · 122 kb · p 1.3e-06 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0181%
Middle Eastern · 1/5,516 alleles
Filtering AF
8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.0005%
8/1,599,066 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0181% | 5,516 |
| Finnishnot grpmax-eligible | 0.00477% | 20,983 |
| European (non-Finnish) | 0.000341% | 293,342 |
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
- ESRRB
- Protein
- p.Arg312Cys
- Coding
- c.934C>T
- MANE Select
- NM_001379180
- dbSNP
- rs1276962033
- Type
- single nucleotide variant
- Location
- chr14:76491530 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.79 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 3 PDB
- Residue 312
- the nr lbd domain; an α-helix; the 'essential for esrrb transcriptional activity and interaction with ncoa3' region
Similar variants
- ESRRB c.851-2A>T Likely pathogenic ★★ same type
- ESRRB c.*1451C>G Likely pathogenic ★★ same type
- ESRRB p.Arg270Ter Likely pathogenic ★★ same type
- ESRRB c.578-4A>G Uncertain significance ★★ same type
- ESRRB c.*1502A>T Uncertain significance ★★ same type
- ESRRB c.*1534C>T Uncertain significance ★★ same type
- ESRRB c.*1550C>A Uncertain significance ★★ same type
- ESRRB c.*1559A>G 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/esrrb-p-arg312cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown