Is EPG5 p.Phe290= (c.870T>C) pathogenic?

EPG5 p.Phe290= (c.870T>C) is classified Likely benign in EPG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-15). Absent from gnomAD v4.1; Associated with Vici syndrome.

What condition is associated with EPG5 p.Phe290= (c.870T>C)?

EPG5 p.Phe290= (c.870T>C) is associated with Vici syndrome (ClinVar).

How common is EPG5 p.Phe290= (c.870T>C) in the general population?

EPG5 p.Phe290= (c.870T>C) is absent from gnomAD v4.1 (gnomAD).

EPG5 p.Phe290=

c.870T>C · rs2050981551 · VCV1108938

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 1.9	GERP -2, phastCons 1
Overall
CADD	8.473	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPG5
Protein: p.Phe290=
Coding: c.870T>C
MANE Select: NM_020964
dbSNP: rs2050981551
Type: single nucleotide variant
Location: chr18:45954532 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.24 · 1 PDB
Residue 290: a UniProt-annotated variant site (in vicis)

Full EPG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Vici syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SIGLEC15 p.Arg290Ser Uncertain significance ★ ⚠ 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-phe290 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown