EPG5 p.Phe684=
c.2052T>C · rs1431174470 · VCV2722853
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
1
Vici syndrome
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 0.93 | GERP -2.2, phastCons 0.97 |
| Overall | ||
| CADD | 6.252 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,046 alleles
Filtering AF
0.00111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0009%
Overall
0.00136%
22/1,614,162 alleles · ultra-rare
exomes 22/1,461,856 · genomes 0/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,046 |
| European (non-Finnish) | 0.00169% | 59,001 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
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.Phe684=
- Coding
- c.2052T>C
- MANE Select
- NM_020964
- dbSNP
- rs1431174470
- Type
- single nucleotide variant
- Location
- chr18:45939647 (GRCh38)
- Gene constraint
- LOEUF 0.58 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.24 · 1 PDB
- Residue 684
- a UniProt-annotated variant site (in vicis)
Similar variants
- 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
- EPG5 p.Arg1161Ter 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-phe684 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown