Is EPG5 p.Ser419fs (c.1254del) pathogenic?

EPG5 p.Ser419fs (c.1254del) is classified Pathogenic in EPG5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-12). Very rare (popmax 0.00224%, amr); Associated with Vici syndrome.

What condition is associated with EPG5 p.Ser419fs (c.1254del)?

EPG5 p.Ser419fs (c.1254del) is associated with Vici syndrome (ClinVar).

How common is EPG5 p.Ser419fs (c.1254del) in the general population?

EPG5 p.Ser419fs (c.1254del) is very rare (popmax 0.00224%, amr) (gnomAD).

EPG5 p.Ser419fs

c.1254del · rs2050902019 · VCV844744

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00224%, amr)

Conditions

Vici syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Overall
CADD	7.979	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% Admixed American · 1/44,612 alleles

Overall 0.000657% 1/152,208 alleles · very rare

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.Ser419fs
Coding: c.1254del
dbSNP: rs2050902019
Type: Deletion
Location: chr18:45951237 (GRCh38)

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

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-ser419fs (accessed [today's date]).

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