Is EDEM3 p.Ser618Ile (c.1853G>T) pathogenic?

EDEM3 p.Ser618Ile (c.1853G>T) is classified Uncertain significance in EDEM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely pathogenic (0.9411); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EDEM3 p.Ser618Ile (c.1853G>T)?

EDEM3 p.Ser618Ile (c.1853G>T) is associated with Inborn genetic diseases (ClinVar).

How common is EDEM3 p.Ser618Ile (c.1853G>T) in the general population?

EDEM3 p.Ser618Ile (c.1853G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDEM3 p.Ser618Ile (c.1853G>T)?

AlphaMissense predicts likely pathogenic (score 0.9411) — an in-silico prediction, not a clinical call.

EDEM3 p.Ser618Ile

c.1853G>T · rs1301893376 · VCV3087178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9411 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9411	likely pathogenic
REVEL	0.524	indeterminate
SaProt	LLR -13.25	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 16 kb · p 0.0044 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ser618Ile
Coding: c.1853G>T
MANE Select: NM_025191
dbSNP: rs1301893376
Type: single nucleotide variant
Location: chr1:184708337 (GRCh38)
Gene constraint: LOEUF 0.671 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.50
Residue 618: 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-ser618ile (accessed [today's date]).

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