Is EDEM3 p.Val96Ile (c.286G>A) pathogenic?

EDEM3 p.Val96Ile (c.286G>A) is classified Uncertain significance in EDEM3 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.0691); Ultra-rare (popmax 0.0329%, mid); Associated with congenital disorder of glycosylation, type 2v.

What condition is associated with EDEM3 p.Val96Ile (c.286G>A)?

EDEM3 p.Val96Ile (c.286G>A) is associated with congenital disorder of glycosylation, type 2v (ClinVar).

How common is EDEM3 p.Val96Ile (c.286G>A) in the general population?

EDEM3 p.Val96Ile (c.286G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is EDEM3-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EDEM3 p.Val96Ile (c.286G>A)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

EDEM3 p.Val96Ile

c.286G>A · VCV3382959

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital disorder of glycosylation, type 2v

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -2.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 4.3, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 20 kb · p 0.23 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00353% 57/1,613,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.0048%	20,825
European (non-Finnish)	0.00407%	24,581
South Asian	0.00329%	30,363
East Asian	0.00223%	44,886

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: EDEM3
Protein: p.Val96Ile
Coding: c.286G>A
MANE Select: NM_025191
Type: single nucleotide variant
Location: chr1:184737630 (GRCh38)
Gene constraint: LOEUF 0.671 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.50

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

Disease context

congenital disorder of glycosylation, type 2v — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For EDEM3-CDG (Orphanet):

Inheritance: Autosomal recessive

Similar variants

EDEM3 p.Val96Ala Uncertain significance ★ ⚠ same residue
EDEM3 p.Asp554Val Uncertain significance ★★ ⚠ same condition
EDEM3 p.Arg265Ter Likely pathogenic ★ same condition
EDEM3 c.1692-28A>T Uncertain significance ★ same condition
EDEM3 c.306-3T>A Uncertain significance ★ same condition
EDEM3 p.Ala99Thr Uncertain significance ★ ⚠ same condition
EDEM3 p.Pro746Ser Benign ★ ⚠ same condition
EDEM3 c.853+1G>T 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/edem3-p-val96ile (accessed [today's date]).

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