ESRRB p.Leu346=
c.1038G>C · VCV4698402
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
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 2.6 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 6.322 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,786 alleles
Filtering AF
0.00624%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00468%
Overall
0.000694%
11/1,584,420 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,310 |
| Admixed American | 0.00186% | 53,622 |
| South Asian | 0.00116% | 86,390 |
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.Leu346=
- Coding
- c.1038G>C
- MANE Select
- NM_001379180
- Type
- single nucleotide variant
- Location
- chr14:76491634 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.79 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 3 PDB
- Residue 346
- 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-leu346 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown