Is EPG5 p.Asp753= (c.2259C>T) pathogenic?

EPG5 p.Asp753= (c.2259C>T) is classified Benign/Likely benign in EPG5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-21). Rare (popmax 0.642%, afr); Associated with Vici syndrome.

What condition is associated with EPG5 p.Asp753= (c.2259C>T)?

EPG5 p.Asp753= (c.2259C>T) is associated with Vici syndrome (ClinVar).

How common is EPG5 p.Asp753= (c.2259C>T) in the general population?

EPG5 p.Asp753= (c.2259C>T) is rare (popmax 0.642%, afr) (gnomAD).

EPG5 p.Asp753=

c.2259C>T · rs142253896 · VCV708842

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.642%, afr)

Conditions

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 2.6	GERP -0.91, phastCons 1
Overall
CADD	9.686	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.642% African / African-American · 469/73,014 alleles

Filtering AF 0.594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.575%

Overall 0.0371% 588/1,584,714 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.642%	156
Admixed American	0.0955%	1,048
Middle Eastern	0.0667%	1,500
Remaining individualsnot grpmax-eligible	0.0423%	2,362
South Asian	0.00947%	10,563
European (non-Finnish)	0.00273%	36,600

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.Asp753=
Coding: c.2259C>T
MANE Select: NM_020964
dbSNP: rs142253896
Type: single nucleotide variant
Location: chr18:45930829 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.24 · 1 PDB
Residue 753: 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-asp753 (accessed [today's date]).

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