ESRRB p.Arg403His
c.1208G>A · rs557399970 · VCV1619682
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.107%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.461 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.6 | GERP 0.064, phastCons 1 |
| Regional constraint | o/e 0.80 | unconstrained · MANE · 122 kb · p 1.3e-06 · regional, not allelic |
| Overall | ||
| CADD | 21.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.107%
South Asian · 97/91,072 alleles
Filtering AF
0.0893%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0829%
Overall
0.00849%
137/1,613,550 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.107% | 939 |
| African / African-American | 0.00799% | 12,511 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,598 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
| European (non-Finnish) | 0.00246% | 40,687 |
| East Asian | 0.00223% | 44,864 |
| Admixed American | 0.00167% | 60,006 |
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.Arg403His
- Coding
- c.1208G>A
- MANE Select
- NM_001379180
- dbSNP
- rs557399970
- Type
- single nucleotide variant
- Location
- chr14:76498301 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.79 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 3 PDB
- Residue 403
- the nr lbd domain; an α-helix; the 'essential for esrrb transcriptional activity and interaction with ncoa3' region
Similar variants
- ESRRB p.Arg403Cys Conflicting classifications of pathogenicity ★ 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-arg403his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown