EPS8 p.Tyr429=
c.1287T>C · rs33956726 · VCV509184
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 5.48%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.87 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -3.1 |
| Overall | ||
| CADD | 0.266 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.48%
African / African-American · 4,110/75,024 alleles
Filtering AF
5.34%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.28%
Overall
1.08%
17,509/1,614,062 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.48% | 18 |
| Middle Eastern | 4.44% | 23 |
| East Asian | 2.71% | 37 |
| South Asian | 2.22% | 45 |
| Admixed American | 2.14% | 47 |
| Remaining individualsnot grpmax-eligible | 1.36% | 74 |
| Ashkenazi Jewishnot grpmax-eligible | 1.24% | 81 |
| European (non-Finnish) | 0.601% | 166 |
| Finnishnot grpmax-eligible | 0.475% | 211 |
| Amishnot grpmax-eligible | 0.11% | 912 |
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.Tyr429=
- Coding
- c.1287T>C
- MANE Select
- NM_004447
- dbSNP
- rs33956726
- Type
- single nucleotide variant
- Location
- chr12:15650970 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 70.77 · 2 PDB
Similar variants
- EPS8 p.Tyr429Cys Uncertain significance ★ ⚠ same residue
- EPS8 c.205-8A>G Uncertain significance ★★ same type
- EPS8 p.Ala150Val Uncertain significance ★★ ⚠ same type
- EPS8 p.Ala219Val 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
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-tyr429 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown