ESRRB p.Met248Val
c.742A>G · rs149642201 · VCV1420503
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00831%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.185 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.80 | unconstrained · MANE · 122 kb · p 1.3e-06 · regional, not allelic |
| Overall | ||
| CADD | 22.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00831%
European (non-Finnish) · 98/1,180,006 alleles
Filtering AF
0.00697%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.0062%
100/1,613,942 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00831% | 12,041 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00134% | 74,882 |
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.Met248Val
- Coding
- c.742A>G
- MANE Select
- NM_001379180
- dbSNP
- rs149642201
- Type
- single nucleotide variant
- Location
- chr14:76482651 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.79 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 3 PDB
- Residue 248
- the nr lbd domain; an α-helix; the 'essential for esrrb transcriptional activity and interaction with ncoa3' region
Similar variants
- ESRRB p.Met248Ile 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-met248val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown