EPG5 p.Phe2526Ser
c.7577T>C · rs559774 · VCV2687932
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 92.9%, 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.15 | GERP -1.2 |
| Overall | ||
| CADD | 9.89 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
92.9%
African / African-American · 38,607/41,548 alleles
Filtering AF
92.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 91.8%
Overall
75.5%
114,937/152,152 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 92.9% | 1 |
| East Asian | 92.2% | 1 |
| Admixed American | 78.4% | 1 |
| Remaining individualsnot grpmax-eligible | 73.3% | 1 |
| South Asian | 69.5% | 1 |
| Finnishnot grpmax-eligible | 68.1% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 66.7% | 1 |
| European (non-Finnish) | 65.5% | 2 |
| Middle Eastern | 65.3% | 2 |
| Amishnot grpmax-eligible | 48.9% | 2 |
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
- EPG5
- Protein
- p.Phe2526Ser
- Coding
- c.7577T>C
- MANE Select
- NM_020964 · reported on NM_001410858
- dbSNP
- rs559774
- Type
- single nucleotide variant
- Location
- chr18:45800871 (GRCh38)
- Gene constraint
- LOEUF 0.58 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.24 · 1 PDB
- Residue 2526
- a UniProt-annotated variant site (in vicis); a UniProt-annotated variant site (in nedpam)
Similar variants
- EPG5 p.Ser2526Ala Uncertain significance ★★ ⚠ same residue
- EPG5 c.1253-1G>A Pathogenic ★★ same type
- EPG5 c.1497+1G>T Pathogenic/Likely pathogenic ★★ same type
- EPG5 c.1678-1G>A Likely pathogenic ★★ same type
- EPG5 c.4475-1G>A Likely pathogenic ★★ same type
- EPG5 c.5304+1G>A Likely pathogenic ★★ same type
- EPG5 c.5869+1G>A Pathogenic ★★ same type
- EPG5 c.6049+5G>A Likely pathogenic ★★ 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/epg5-p-phe2526ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown