Is ALG3 p.Gly55= (c.165C>T) pathogenic?

ALG3 p.Gly55= (c.165C>T) is classified Pathogenic/Likely pathogenic in ALG3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-21). Very rare (popmax 0.00608%, nfe); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Gly55= (c.165C>T)?

ALG3 p.Gly55= (c.165C>T) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Gly55= (c.165C>T) in the general population?

ALG3 p.Gly55= (c.165C>T) is very rare (popmax 0.00608%, nfe) (gnomAD).

How is ALG3-CDG inherited?

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

ALG3 p.Gly55=

c.165C>T · rs387906273 · VCV2128

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00608%, nfe)

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	0.328	indeterminate
Splicing
SpliceAI	Δ0.84	donor loss, 31 bp away · masked 0 · deltas
Pangolin	Δ0.49	loss · gain 0.41 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.5	GERP 1.5, phastCons 1
Overall
CADD	12.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00608% European (non-Finnish) · 62/1,019,152 alleles

Filtering AF 0.00484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00478% 65/1,359,810 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00608%	16,438
Remaining individualsnot grpmax-eligible	0.00436%	22,958
South Asian	0.00114%	87,576

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.Gly55=
Coding: c.165C>T
MANE Select: NM_005787
dbSNP: rs387906273
Type: single nucleotide variant
Location: chr3:184248776 (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 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.Ile69Thr Likely pathogenic ★★ same condition
ALG3 p.Met1Thr 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-gly55 (accessed [today's date]).

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