ESR1 p.Cys240=
c.720C>T · rs200303616 · VCV2602795
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0326%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.124 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.55 | GERP -1.7, phastCons 0.023 |
| Overall | ||
| CADD | 7.385 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0326%
European (non-Finnish) · 384/1,177,746 alleles
Filtering AF
0.0299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0288%
Overall
0.0263%
424/1,611,692 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0326% | 3,067 |
| Finnishnot grpmax-eligible | 0.0234% | 4,268 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,459 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0203% | 4,931 |
| African / African-American | 0.004% | 25,004 |
| Admixed American | 0.00333% | 30,016 |
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
- ESR1
- Protein
- p.Cys240=
- Coding
- c.720C>T
- MANE Select
- NM_000125
- dbSNP
- rs200303616
- Type
- single nucleotide variant
- Location
- chr6:151880731 (GRCh38)
- Gene constraint
- LOEUF 0.456 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.14 · 492 PDB
- Residue 240
- a DNA-binding region; an α-helix; the 'mediates interaction with dnttip2' region
Similar variants
- SYNE1 p.Arg8746Ter Pathogenic/Likely pathogenic ★★ same type
- ESR1 p.Lys299Arg Uncertain significance ★★ ⚠ same type
- SYNE1 p.Arg8735Leu Uncertain significance ★★ ⚠ same type
- SYNE1 p.Arg8738His Uncertain significance ★★ ⚠ same type
- SYNE1 p.Arg8746Gln Uncertain significance ★★ same type
- SYNE1 p.Arg8782Gln Uncertain significance ★★ same type
- SYNE1 p.Arg8782Gly Uncertain significance ★★ same type
- SYNE1 p.Asp8725Asn 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/esr1-p-cys240 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown