Is ALG3 p.Gly197= (c.591T>C) pathogenic?

ALG3 p.Gly197= (c.591T>C) is classified Benign in ALG3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Common (popmax 13.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Gly197= (c.591T>C)?

ALG3 p.Gly197= (c.591T>C) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How is ALG3-CDG inherited?

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

ALG3 p.Gly197=

Q: How common is ALG3 p.Gly197= (c.591T>C) in the general population?

ALG3 p.Gly197= (c.591T>C) is common (popmax 13.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.591T>C · rs2233464 · VCV344355

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 13.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

ALG3-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.75, phastCons 1
Overall
CADD	11.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.5% African / African-American · 10,135/74,868 alleles

Filtering AF 13.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.2%

Overall 0.721% 11,633/1,613,624 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.5%	7
Admixed American	0.937%	107
Remaining individualsnot grpmax-eligible	0.896%	112
Middle Eastern	0.512%	195
European (non-Finnish)	0.0271%	3,687
South Asian	0.0264%	3,794
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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.Gly197=
Coding: c.591T>C
MANE Select: NM_005787
dbSNP: rs2233464
Type: single nucleotide variant
Location: chr3:184245212 (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.Gly55= Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Ile69Thr 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-gly197 (accessed [today's date]).

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