EMSY p.Arg221=
c.661C>A · rs61741528 · VCV786204
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.07%, 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 3.3 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 12.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.07%
African / African-American · 3,055/75,002 alleles
Filtering AF
3.95%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.9%
Overall
0.259%
4,185/1,614,096 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.07% | 25 |
| Ashkenazi Jewishnot grpmax-eligible | 1.26% | 79 |
| Remaining individualsnot grpmax-eligible | 0.43% | 232 |
| Admixed American | 0.333% | 300 |
| Middle Eastern | 0.181% | 551 |
| European (non-Finnish) | 0.023% | 4,354 |
| South Asian | 0.00659% | 15,179 |
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
- EMSY
- Protein
- p.Arg221=
- Coding
- c.661C>A
- MANE Select
- NM_001300942
- dbSNP
- rs61741528
- Type
- single nucleotide variant
- Location
- chr11:76463865 (GRCh38)
- Gene constraint
- LOEUF 0.262 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 42.40 · 3 PDB
- Residue 221
- the 'interaction with brca2' region
Similar variants
- EMSY c.1730-7T>C Benign/Likely benign ★★ same type
- EMSY c.71-7C>T Benign ★★ same type
- EMSY p.Gln988= Benign ★★ same type
- EMSY p.Leu969Arg Benign ★★ same type
- EMSY c.1730-5C>G Uncertain significance ★ same type
- EMSY p.Gln1060Ter Uncertain significance ★ same type
- EMSY p.Gln1090Lys Uncertain significance ★ ⚠ same type
- EMSY p.Gln1260Arg 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/emsy-p-arg221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown