Is EPG5 p.Pro583= (c.1749C>T) pathogenic?

EPG5 p.Pro583= (c.1749C>T) is classified Likely benign in EPG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-28). Very rare (popmax 0.000848%, nfe); Associated with Vici syndrome.

What condition is associated with EPG5 p.Pro583= (c.1749C>T)?

EPG5 p.Pro583= (c.1749C>T) is associated with Vici syndrome (ClinVar).

How common is EPG5 p.Pro583= (c.1749C>T) in the general population?

EPG5 p.Pro583= (c.1749C>T) is very rare (popmax 0.000848%, nfe) (gnomAD).

EPG5 p.Pro583=

c.1749C>T · rs746257883 · VCV755876

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

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	GERP -3.2, phastCons 0.002
Overall
CADD	4.261	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,838 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00062% 10/1,613,812 alleles · very rare exomes 8/1,461,648 · genomes 2/152,164 · joint denominator

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.Pro583=
Coding: c.1749C>T
MANE Select: NM_020964
dbSNP: rs746257883
Type: single nucleotide variant
Location: chr18:45944048 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.24 · 1 PDB
Residue 583: 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

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-pro583 (accessed [today's date]).

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