Is ALG1 p.Gly134fs (c.398_399insCA) pathogenic?

ALG1 p.Gly134fs (c.398399insCA) is classified Pathogenic in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-08). Absent from gnomAD; Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Gly134fs (c.398_399insCA)?

ALG1 p.Gly134fs (c.398_399insCA) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Gly134fs (c.398_399insCA) in the general population?

ALG1 p.Gly134fs (c.398_399insCA) is absent from gnomAD (gnomAD).

How is ALG1-CDG inherited?

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

ALG1 p.Gly134fs

c.398_399insCA · rs1956891979 · VCV1400583

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ALG1-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 4 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALG1
Protein: p.Gly134fs
Coding: c.398_399insCA
MANE Select: NM_019109
dbSNP: rs1956891979
Type: Insertion
Location: chr16:5075395 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG1 p.Gly134Ala Uncertain significance ★★ ⚠ same residue
ALG1 p.Gly134Ser Uncertain significance ★ ⚠ same residue
ALG1 p.Ala418fs Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.208+19_208+20insTATG Uncertain significance ★★ same condition
ALG1 c.208+17_208+18insCGTC Likely benign ★ same condition
ALG1 c.208+18_208+19insATCT Likely benign ★ same condition
ALG1 c.208+19_208+20insTTTG Likely benign ★ same condition
ALG1 c.1187+1G>A 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/alg1-p-gly134fs (accessed [today's date]).

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