ESS2 p.Arg127=
c.381C>T · rs146347276 · VCV729427
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.017%, amr)
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 -2.2 | GERP -2.6 |
| Overall | ||
| CADD | 2.543 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.017%
Admixed American · 10/58,714 alleles
Filtering AF
0.00918%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00707%
Overall
0.00783%
126/1,609,352 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.017% | 5,871 |
| European (non-Finnish) | 0.009% | 11,117 |
| African / African-American | 0.0067% | 14,925 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,745 |
| South Asian | 0.00221% | 45,219 |
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
- ESS2
- Protein
- p.Arg127=
- Coding
- c.381C>T
- MANE Select
- NM_022719
- dbSNP
- rs146347276
- Type
- single nucleotide variant
- Location
- chr22:19142557 (GRCh38)
- Gene constraint
- LOEUF 0.844 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.41 · 5 PDB
- Residue 127
- the 'disordered' region
Similar variants
- ESS2 p.Arg127Cys Uncertain significance ★ ⚠ same residue
- ESS2 p.Arg127His Uncertain significance ★ ⚠ same residue
- ESS2 p.Arg175Gln Uncertain significance ★★ ⚠ same type
- ESS2 p.Asn311= Benign ★★ same type
- ESS2 p.Glu234Lys Benign ★★ same type
- ESS2 p.His178= Likely benign ★★ same type
- ESS2 p.Lys66= Benign/Likely benign ★★ same type
- ESS2 p.Pro99Leu Benign ★★ 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/ess2-p-arg127 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown