EPG5 p.Pro247=
c.741G>A · rs765449856 · VCV797506
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
1
Vici syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -3.2 |
| Overall | ||
| CADD | 12.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.0013%
21/1,614,072 alleles · ultra-rare
exomes 20/1,461,882 · genomes 1/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.00333% | 30,004 |
| Finnishnot grpmax-eligible | 0.00156% | 64,020 |
| European (non-Finnish) | 0.00136% | 73,752 |
| South Asian | 0.0011% | 91,084 |
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.Pro247=
- Coding
- c.741G>A
- MANE Select
- NM_020964
- dbSNP
- rs765449856
- Type
- single nucleotide variant
- Location
- chr18:45954661 (GRCh38)
- Gene constraint
- LOEUF 0.58 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.24 · 1 PDB
- Residue 247
- a UniProt-annotated variant site (in vicis)
Similar variants
- EPG5 p.Pro247Leu Benign/Likely benign ★★ same residue
- EPG5 c.1253-1G>A Pathogenic ★★ same condition
- EPG5 c.1497+1G>T Pathogenic/Likely pathogenic ★★ same condition
- EPG5 c.1678-1G>A Likely pathogenic ★★ same condition
- EPG5 c.4475-1G>A Likely pathogenic ★★ same condition
- EPG5 c.5304+1G>A Likely pathogenic ★★ same condition
- EPG5 c.5869+1G>A Pathogenic ★★ same condition
- EPG5 c.6049+5G>A Likely pathogenic ★★ same condition
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-pro247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown