ESR2 p.Glu211=
c.633A>G · rs74808355 · VCV787181
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.217%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.50 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.21 | gain · loss 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 0.14, phastCons 1 |
| Overall | ||
| CADD | 16.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.217%
European (non-Finnish) · 2,552/1,178,084 alleles
Filtering AF
0.21%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.207%
Overall
0.18%
2,901/1,612,042 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.217% | 462 |
| Admixed American | 0.178% | 561 |
| Remaining individualsnot grpmax-eligible | 0.157% | 637 |
| Middle Eastern | 0.132% | 758 |
| Finnishnot grpmax-eligible | 0.126% | 791 |
| African / African-American | 0.0387% | 2,586 |
| South Asian | 0.0264% | 3,793 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,796 |
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
- ESR2
- Protein
- p.Glu211=
- Coding
- c.633A>G
- MANE Select
- NM_001437
- dbSNP
- rs74808355
- Type
- single nucleotide variant
- Location
- chr14:64268814 (GRCh38)
- Gene constraint
- LOEUF 1.002 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.76 · 39 PDB
- Residue 211
- a DNA-binding region
Similar variants
- ESR2 p.Ala432Thr Uncertain significance ★★ ⚠ same type
- ESR2 p.Arg230Gln Uncertain significance ★★ ⚠ same type
- ESR2 p.Arg346Cys Uncertain significance ★★ ⚠ same type
- ESR2 p.Arg388Gln Uncertain significance ★★ ⚠ same type
- ESR2 p.Asn407Ser Uncertain significance ★★ ⚠ same type
- ESR2 p.Asp154Asn Uncertain significance ★★ ⚠ same type
- ESR2 p.Cys169Phe Uncertain significance ★★ ⚠ same type
- ESR2 p.Gly243Asp 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/esr2-p-glu211 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown