EPS8 p.Ala219=
c.657G>A · VCV4692960
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, 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 -5.7 | GERP -5 |
| Overall | ||
| CADD | 2.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
European (non-Finnish) · 158/1,179,876 alleles
Filtering AF
0.0116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.011%
Overall
0.0102%
165/1,613,668 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0134% | 7,468 |
| South Asian | 0.00439% | 22,760 |
| Admixed American | 0.00167% | 59,920 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
| African / African-American | 0.00134% | 74,902 |
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
- EPS8
- Protein
- p.Ala219=
- Coding
- c.657G>A
- MANE Select
- NM_004447
- Type
- single nucleotide variant
- Location
- chr12:15665835 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 70.77 · 2 PDB
- Residue 219
- the 'disordered' region
Similar variants
- EPS8 p.Ala219Val Uncertain significance ★★ ⚠ same residue
- EPS8 c.205-8A>G Uncertain significance ★★ same type
- EPS8 p.Ala150Val Uncertain significance ★★ ⚠ same type
- EPS8 p.Ala416Asp Uncertain significance ★★ ⚠ same type
- EPS8 p.Arg195Trp Uncertain significance ★★ ⚠ same type
- EPS8 p.Arg403Trp Uncertain significance ★★ ⚠ same type
- EPS8 p.Arg432Gln Uncertain significance ★★ ⚠ same type
- EPS8 p.Arg434Cys 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/eps8-p-ala219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown