Is ALG12 c.*1G>C pathogenic?

ALG12 c.1G>C is classified Uncertain significance in ALG12 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-01-12). Rare (popmax 0.386%, nfe); Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 c.*1G>C?

ALG12 c.*1G>C is associated with ALG12-congenital disorder of glycosylation (ClinVar).

How common is ALG12 c.*1G>C in the general population?

ALG12 c.*1G>C is rare (popmax 0.386%, nfe) (gnomAD).

How is ALG12-CDG inherited?

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

ALG12 c.*1G>C

rs138804791 · VCV166673

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.386%, nfe)

Conditions

ALG12-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.077	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -0.85
Non-coding constraint	Z 3.29	1 kb window · o/e 0.66 · regional · uncalibrated
Overall
CADD	5.797	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.386% European (non-Finnish) · 4,555/1,180,020 alleles

Filtering AF 0.377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.373%

Overall 0.31% 5,010/1,614,178 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.386%	259
Remaining individualsnot grpmax-eligible	0.269%	372
Admixed American	0.237%	423
Middle Eastern	0.181%	551
South Asian	0.0681%	1,469
African / African-American	0.052%	1,925
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,114
Finnishnot grpmax-eligible	0.0281%	3,557
East Asian	0.00223%	44,870

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: ALG12
Coding: c.*1G>C
MANE Select: NM_024105
dbSNP: rs138804791
Type: single nucleotide variant
Location: chr22:49903837 (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 c.295+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG12 c.768+1G>A Likely pathogenic ★★ same condition
ALG12 p.Arg146Gln Pathogenic/Likely pathogenic ★★ same condition
ALG12 p.Arg202Ter Pathogenic/Likely pathogenic ★★ same condition
ALG12 p.Gly101Arg Likely pathogenic ★★ same condition
ALG12 p.Thr67Met Pathogenic/Likely pathogenic ★★ same condition
ALG12 c.469+5G>A Uncertain significance ★★ same condition
ALG12 c.470-3C>T 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-c-star-1g-c (accessed [today's date]).

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