Is ALG3 p.Val362Ile (c.1084G>A) pathogenic?

ALG3 p.Val362Ile (c.1084G>A) is classified Conflicting classifications of pathogenicity in ALG3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.0981); Rare (popmax 0.548%, eas); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Val362Ile (c.1084G>A)?

ALG3 p.Val362Ile (c.1084G>A) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Val362Ile (c.1084G>A) in the general population?

ALG3 p.Val362Ile (c.1084G>A) is rare (popmax 0.548%, eas) (gnomAD).

How is ALG3-CDG inherited?

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

What do computational predictors say about ALG3 p.Val362Ile (c.1084G>A)?

AlphaMissense predicts likely benign (score 0.0981) — an in-silico prediction, not a clinical call.

ALG3 p.Val362Ile

c.1084G>A · rs186946267 · VCV344348

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0981 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.548%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALG3-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0981	likely benign
REVEL	0.508	indeterminate
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 2,165 bp · p 0.0031 · regional, not allelic
Overall
CADD	25.3	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

Grpmax group 0.548% East Asian · 246/44,890 alleles

Filtering AF 0.492% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.47%

Overall 0.14% 2,263/1,613,810 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.548%	182
Remaining individualsnot grpmax-eligible	0.195%	512
European (non-Finnish)	0.151%	661
Ashkenazi Jewishnot grpmax-eligible	0.0709%	1,410
Finnishnot grpmax-eligible	0.0501%	1,996
South Asian	0.0351%	2,846
Admixed American	0.0217%	4,616
African / African-American	0.0147%	6,822

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: ALG3
Protein: p.Val362Ile
Coding: c.1084G>A
MANE Select: NM_005787
dbSNP: rs186946267
Type: single nucleotide variant
Location: chr3:184242883 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.05

Full ALG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG3-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG3 p.Val362Gly Uncertain significance ★ ⚠ same residue
ALG3 c.444+1G>T Likely pathogenic ★★ same condition
ALG3 p.Arg171Gln Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Arg266Cys Pathogenic ★★ same condition
ALG3 p.Arg354Cys Likely pathogenic ★★ same condition
ALG3 p.Arg354His Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Asn174Ser Likely pathogenic ★★ ⚠ same condition
ALG3 p.Gly55= Pathogenic/Likely 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/alg3-p-val362ile (accessed [today's date]).

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