ESRRB p.Arg343Trp
c.1027C>T · rs143118664 · VCV1065107
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.711 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.82 | GERP 1.3, phastCons 1 |
| Regional constraint | o/e 0.80 | unconstrained · MANE · 122 kb · p 1.3e-06 · regional, not allelic |
| Overall | ||
| CADD | 23.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.0865% | 1,156 |
| East Asiangrpmax | 0.0205% | 4,883 |
| Remaining individualsnot grpmax-eligible | 0.0195% | 5,128 |
| Middle Eastern | 0.0179% | 5,576 |
| Admixed American | 0.00932% | 10,733 |
| European (non-Finnish) | 0.00643% | 15,550 |
| Finnishnot grpmax-eligible | 0.00484% | 20,659 |
| South Asian | 0.00463% | 21,618 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg343Trp
- Coding
- c.1027C>T
- MANE Select
- NM_001379180
- dbSNP
- rs143118664
- Type
- single nucleotide variant
- Location
- chr14:76491623 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.79 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 3 PDB
- Residue 343
- the nr lbd domain; an α-helix; the 'essential for esrrb transcriptional activity and interaction with ncoa3' region
Similar variants
- ESRRB p.Arg343Gln Uncertain significance ★★ same residue
- ESRRB p.Arg200His Uncertain significance ★ same condition
- 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
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-arg343trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown