ESS2 p.Pro228=
c.684A>C · rs1601357135 · VCV737618
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
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 -6.2 | GERP -2.6 |
| Overall | ||
| CADD | 3.891 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,336 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000205%
3/1,461,124 alleles · very rare
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.Pro228=
- Coding
- c.684A>C
- MANE Select
- NM_022719
- dbSNP
- rs1601357135
- Type
- single nucleotide variant
- Location
- chr22:19139616 (GRCh38)
- Gene constraint
- LOEUF 0.844 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.41 · 5 PDB
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.Thr460= Likely 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-pro228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown