ESRRB p.Pro242=
c.726G>A · rs370195063 · VCV179278
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0936%, eas)
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 -14 | GERP -4.3 |
| Overall | ||
| CADD | 0.019 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0936%
East Asian · 42/44,858 alleles
Filtering AF
0.0712%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0632%
Overall
0.0083%
134/1,614,070 alleles · ultra-rare
exomes 110/1,461,878 · genomes 24/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0936% | 1,068 |
| African / African-American | 0.0187% | 5,358 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,419 |
| European (non-Finnish) | 0.00559% | 17,879 |
| Admixed American | 0.005% | 20,002 |
| South Asian | 0.0022% | 45,533 |
| Finnishnot grpmax-eligible | 0.00156% | 64,018 |
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.Pro242=
- Coding
- c.726G>A
- MANE Select
- NM_001379180
- dbSNP
- rs370195063
- Type
- single nucleotide variant
- Location
- chr14:76482635 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.79 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 3 PDB
- Residue 242
- the nr lbd domain; an α-helix; the 'essential for esrrb transcriptional activity and interaction with ncoa3' region
Similar variants
- ESRRB p.Pro242Leu Uncertain significance ★ same residue
- 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
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-pro242 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown