Is EPG5 p.Thr1237Arg (c.3710C>G) pathogenic?

EPG5 p.Thr1237Arg (c.3710C>G) is classified Uncertain significance in EPG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: ambiguous (0.4271); Absent from gnomAD v4.1; Associated with Vici syndrome.

What condition is associated with EPG5 p.Thr1237Arg (c.3710C>G)?

EPG5 p.Thr1237Arg (c.3710C>G) is associated with Vici syndrome (ClinVar).

How common is EPG5 p.Thr1237Arg (c.3710C>G) in the general population?

EPG5 p.Thr1237Arg (c.3710C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPG5 p.Thr1237Arg (c.3710C>G)?

AlphaMissense predicts ambiguous (score 0.4271) — an in-silico prediction, not a clinical call.

EPG5 p.Thr1237Arg

c.3710C>G · VCV4739825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4271 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Vici syndrome

Computational evidence

Protein change
AlphaMissense	0.4271	ambiguous
REVEL	0.119	moderately benign-leaning
SaProt	LLR -11.11	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.38	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP -0.078, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 3,183 bp · p 0.00018 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Thr1237Arg
Coding: c.3710C>G
MANE Select: NM_020964
Type: single nucleotide variant
Location: chr18:45913812 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.24 · 1 PDB
Residue 1237: a UniProt-annotated variant site (in vicis); a UniProt-annotated variant site (in nedpam)

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-thr1237arg (accessed [today's date]).

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