ESS2 p.Thr460=
c.1380G>A · rs373680781 · VCV725854
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.116%, sas)
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 -13 | GERP -2.2 |
| Overall | ||
| CADD | 4.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.116%
South Asian · 98/84,518 alleles
Filtering AF
0.0974%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0904%
Overall
0.00914%
142/1,554,204 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.116% | 862 |
| Middle Eastern | 0.0352% | 2,838 |
| Admixed American | 0.0135% | 7,402 |
| Finnishnot grpmax-eligible | 0.00962% | 10,396 |
| Remaining individualsnot grpmax-eligible | 0.00336% | 29,795 |
| European (non-Finnish) | 0.00235% | 42,497 |
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.Thr460=
- Coding
- c.1380G>A
- MANE Select
- NM_022719
- dbSNP
- rs373680781
- Type
- single nucleotide variant
- Location
- chr22:19134247 (GRCh38)
- Gene constraint
- LOEUF 0.844 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.41 · 5 PDB
- Residue 460
- the 'disordered' region
Similar variants
- 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
- ESS2 p.Ser7Ala Benign ★★ same type
- ESS2 p.Ala115Gly 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/ess2-p-thr460 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown