ESRRA p.Ser27=
c.81G>A · rs377634093 · VCV746573
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, 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 -0.46 | GERP -3, phastCons 0.002 |
| Overall | ||
| CADD | 7.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,896 alleles
Filtering AF
0.002%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00176%
Overall
0.00267%
43/1,613,418 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,965 |
| African / African-American | 0.00534% | 18,728 |
| European (non-Finnish) | 0.0028% | 35,752 |
| Admixed American | 0.00167% | 59,972 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,442 |
| South Asian | 0.0011% | 91,000 |
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
- ESRRA
- Protein
- p.Ser27=
- Coding
- c.81G>A
- MANE Select
- NM_004451
- dbSNP
- rs377634093
- Type
- single nucleotide variant
- Location
- chr11:64307260 (GRCh38)
- Gene constraint
- LOEUF 0.458 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 78.25 · 6 PDB
- Residue 27
- the 'repressor domain' region; the 'disordered' region
Similar variants
- ESRRA p.Ser27Leu Uncertain significance ★ ⚠ same residue
- ESRRA p.Thr31Ile Benign ★★ ⚠ same type
- ESRRA p.Ala184Thr Uncertain significance ★ ⚠ same type
- ESRRA p.Ala216Thr Uncertain significance ★ ⚠ same type
- ESRRA p.Ala226Gly Uncertain significance ★ ⚠ same type
- ESRRA p.Ala274Gly Uncertain significance ★ ⚠ same type
- ESRRA p.Ala300Gly Uncertain significance ★ ⚠ same type
- ESRRA p.Ala367Thr 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/esrra-p-ser27 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown