Is EPG5 p.Pro111= (c.333C>T) pathogenic?

EPG5 p.Pro111= (c.333C>T) is classified Likely benign in EPG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). Very rare (popmax 8.47e-05%, nfe); Associated with Vici syndrome.

What condition is associated with EPG5 p.Pro111= (c.333C>T)?

EPG5 p.Pro111= (c.333C>T) is associated with Vici syndrome (ClinVar).

How common is EPG5 p.Pro111= (c.333C>T) in the general population?

EPG5 p.Pro111= (c.333C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

EPG5 p.Pro111=

c.333C>T · rs2512130184 · VCV2768627

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 0.51	GERP -1.6, phastCons 0.002
Overall
CADD	4.258	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,988 alleles

Overall 6.2e-05% 1/1,614,072 alleles · very rare exomes 1/1,461,766 · genomes 0/152,306 · 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.Pro111=
Coding: c.333C>T
MANE Select: NM_020964
dbSNP: rs2512130184
Type: single nucleotide variant
Location: chr18:45955069 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.24 · 1 PDB
Residue 111: a UniProt-annotated variant site (in vicis); the 'disordered' region

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.His111Gln 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-pro111 (accessed [today's date]).

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