Is EDEM3 p.Pro536Arg (c.1607C>G) pathogenic?

EDEM3 p.Pro536Arg (c.1607C>G) is classified Uncertain significance in EDEM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: ambiguous (0.4969); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EDEM3 p.Pro536Arg (c.1607C>G)?

EDEM3 p.Pro536Arg (c.1607C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EDEM3 p.Pro536Arg (c.1607C>G) in the general population?

EDEM3 p.Pro536Arg (c.1607C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDEM3 p.Pro536Arg (c.1607C>G)?

AlphaMissense predicts ambiguous (score 0.4969) — an in-silico prediction, not a clinical call.

EDEM3 p.Pro536Arg

c.1607C>G · rs1650252385 · VCV2545209

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4969	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -6.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 2,044 bp · p 0.22 · regional, not allelic
Overall
CADD	25.9	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: EDEM3
Protein: p.Pro536Arg
Coding: c.1607C>G
MANE Select: NM_025191
dbSNP: rs1650252385
Type: single nucleotide variant
Location: chr1:184711807 (GRCh38)
Gene constraint: LOEUF 0.671 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.50
Residue 536: a UniProt-annotated variant site (in cdg2v; uncertain significance)

Full EDEM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EDEM3 p.Arg579Lys Uncertain significance ★★ ⚠ same condition
EDEM3 p.Asn691Ser Uncertain significance ★★ ⚠ same condition
EDEM3 p.His454Gln Uncertain significance ★★ ⚠ same condition
EDEM3 p.Pro574Ser Uncertain significance ★★ ⚠ same condition
EDEM3 p.Ala17Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
EDEM3 p.Ala245Thr Uncertain significance ★ ⚠ same condition
EDEM3 p.Ala41Val Uncertain significance ★ ⚠ same condition
EDEM3 p.Ala437Ser Uncertain significance ★ ⚠ 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/edem3-p-pro536arg (accessed [today's date]).

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