Is ALG3 c.196+19del pathogenic?

ALG3 c.196+19del is classified Likely benign in ALG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-25). Ultra-rare (popmax 0.0179%, amr); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 c.196+19del?

ALG3 c.196+19del is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 c.196+19del in the general population?

ALG3 c.196+19del is ultra-rare (popmax 0.0179%, amr) (gnomAD).

How is ALG3-CDG inherited?

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

ALG3 c.196+19del

rs1260750286 · VCV1592152

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, amr)

Conditions

ALG3-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +19	near-intronic (+19 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.56	GERP -3.3
Non-coding constraint	Z 0.64	1 kb window · o/e 0.96 · regional · uncalibrated
Overall
CADD	13.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0179% Admixed American · 9/50,248 alleles

Filtering AF 0.00929% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00697%

Overall 0.00132% 20/1,509,558 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0179%	5,583
Remaining individualsnot grpmax-eligible	0.00515%	19,412
Ashkenazi Jewishnot grpmax-eligible	0.0039%	25,630
European (non-Finnish)	0.00063%	158,815

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
Coding: c.196+19del
MANE Select: NM_005787
dbSNP: rs1260750286
Type: Deletion
Location: chr3:184248726 (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.His297fs Pathogenic ★ same condition
ALG3 p.Lys72fs Likely pathogenic ★ same condition
ALG3 p.Pro39fs Pathogenic ★ same condition
ALG3 c.933-20_933-17del Likely benign ★ same condition
ALG3 c.163_196+3del Pathogenic same condition
ALG3 c.444+1G>T Likely pathogenic ★★ same condition
ALG3 p.Arg171Gln Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Arg266Cys 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-c-196-plus-19del (accessed [today's date]).

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