Is ALG12 p.Thr288fs (c.861del) pathogenic?

ALG12 p.Thr288fs (c.861del) is classified Pathogenic in ALG12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 p.Thr288fs (c.861del)?

ALG12 p.Thr288fs (c.861del) is associated with ALG12-congenital disorder of glycosylation (ClinVar).

How is ALG12-CDG inherited?

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

ALG12 p.Thr288fs

c.861del · VCV4697444

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ALG12-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.66	GERP -3.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ALG12
Protein: p.Thr288fs
Coding: c.861del
MANE Select: NM_024105
Type: Deletion
Location: chr22:49907852 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.26

Full ALG12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG12-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG12-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG12 p.Thr288Met Conflicting classifications of pathogenicity ★ ⚠ same residue
ALG12 p.Thr288= Likely benign ★ same residue
ALG12 p.Arg311fs Pathogenic ★★ same condition
ALG12 p.Asn334fs Pathogenic/Likely pathogenic ★★ same condition
ALG12 p.Gln40fs Pathogenic ★★ same condition
ALG12 p.Leu12fs Pathogenic/Likely pathogenic ★★ same condition
ALG12 p.Lys416fs Likely pathogenic ★★ same condition
ALG12 p.Arg486fs Uncertain significance ★★ 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/alg12-p-thr288fs (accessed [today's date]).

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