EPS8 p.Ala488=
c.1464C>T · VCV4697579
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.03%, 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 -1.7 | GERP -4.8 |
| Overall | ||
| CADD | 0.216 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.03%
Admixed American · 18/59,916 alleles
Filtering AF
0.0194%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.016%
Overall
0.00167%
27/1,613,432 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.03% | 3,329 |
| East Asian | 0.00223% | 44,884 |
| African / African-American | 0.00133% | 74,920 |
| European (non-Finnish) | 0.000593% | 168,520 |
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.Ala488=
- Coding
- c.1464C>T
- MANE Select
- NM_004447
- Type
- single nucleotide variant
- Location
- chr12:15647231 (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 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
- 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-ala488 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown