ESRRB p.Ala424=
c.1272C>T · rs563575581 · VCV2172874
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0268%, eas)
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 -13 | GERP -4.4 |
| Overall | ||
| CADD | 5.626 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0268%
East Asian · 12/44,850 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00267%
43/1,612,812 alleles · ultra-rare
exomes 39/1,460,476 · genomes 4/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0268% | 3,737 |
| African / African-American | 0.00666% | 15,007 |
| European (non-Finnish) | 0.00212% | 47,187 |
| Admixed American | 0.00167% | 59,870 |
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.Ala424=
- Coding
- c.1272C>T
- MANE Select
- NM_001379180
- dbSNP
- rs563575581
- Type
- single nucleotide variant
- Location
- chr14:76498365 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.79 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 3 PDB
- Residue 424
- 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-ala424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown