Is ALG3 p.Tyr361= (c.1083C>T) pathogenic?

ALG3 p.Tyr361= (c.1083C>T) is classified Uncertain significance in ALG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). Ultra-rare (popmax 0.016%, afr); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Tyr361= (c.1083C>T)?

ALG3 p.Tyr361= (c.1083C>T) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Tyr361= (c.1083C>T) in the general population?

ALG3 p.Tyr361= (c.1083C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

How is ALG3-CDG inherited?

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

ALG3 p.Tyr361=

c.1083C>T · rs374164530 · VCV2058076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

ALG3-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.329	indeterminate
Splicing
SpliceAI	Δ0.22	acceptor loss, 24 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.46	GERP -3.8, phastCons 0.002
Overall
CADD	4.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,946 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.000992% 16/1,613,712 alleles · ultra-rare exomes 11/1,461,470 · genomes 5/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,246
Remaining individualsnot grpmax-eligible	0.0016%	62,462
European (non-Finnish)	0.000254%	393,278

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.Tyr361=
Coding: c.1083C>T
MANE Select: NM_005787
dbSNP: rs374164530
Type: single nucleotide variant
Location: chr3:184242884 (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.Tyr361Ser 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-tyr361 (accessed [today's date]).

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