Is ALG1 p.Tyr103Ter (c.309C>G) pathogenic?

ALG1 p.Tyr103Ter (c.309C>G) is classified Pathogenic in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). Absent from gnomAD v4.1; Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Tyr103Ter (c.309C>G)?

ALG1 p.Tyr103Ter (c.309C>G) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Tyr103Ter (c.309C>G) in the general population?

ALG1 p.Tyr103Ter (c.309C>G) is absent from gnomAD v4.1 (gnomAD).

How is ALG1-CDG inherited?

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

ALG1 p.Tyr103Ter

c.309C>G · rs199553558 · VCV1416621

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 13
Splicing
SpliceAI	Δ0.41	acceptor loss, 22 bp away · masked 0 · deltas
Pangolin	Δ0.55	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -10	GERP -3.3
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALG1
Protein: p.Tyr103Ter
Coding: c.309C>G
MANE Select: NM_019109
dbSNP: rs199553558
Type: single nucleotide variant
Location: chr16:5073175 (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.Tyr103= Likely benign ★★ same residue
ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.1187+2T>C Pathogenic ★★ same condition
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.209-2A>G Likely pathogenic ★★ same condition
ALG1 c.539+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.630-2A>G Likely pathogenic ★★ same condition
ALG1 c.863-2A>G 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-tyr103ter (accessed [today's date]).

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