Is ALG12 p.Arg184Gly (c.550A>G) pathogenic?

ALG12 p.Arg184Gly (c.550A>G) is classified Uncertain significance in ALG12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely pathogenic (0.924); Very rare (popmax 0.00203%, nfe); Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 p.Arg184Gly (c.550A>G)?

ALG12 p.Arg184Gly (c.550A>G) is associated with ALG12-congenital disorder of glycosylation (ClinVar).

How common is ALG12 p.Arg184Gly (c.550A>G) in the general population?

ALG12 p.Arg184Gly (c.550A>G) is very rare (popmax 0.00203%, nfe) (gnomAD).

How is ALG12-CDG inherited?

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

What do computational predictors say about ALG12 p.Arg184Gly (c.550A>G)?

AlphaMissense predicts likely pathogenic (score 0.924) — an in-silico prediction, not a clinical call.

ALG12 p.Arg184Gly

c.550A>G · rs1569176254 · VCV1401757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG12-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.924	likely pathogenic · top 5% in ALG12
REVEL	0.731	pathogenic-leaning
SaProt	LLR -13.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -3.2, phastCons 0.88
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,179,962 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00149% 24/1,613,658 alleles · very rare

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
Protein: p.Arg184Gly
Coding: c.550A>G
MANE Select: NM_024105
dbSNP: rs1569176254
Type: single nucleotide variant
Location: chr22:49910008 (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.Arg184Thr Uncertain significance ★ ⚠ same residue
ZBED4 p.Ser184Phe Uncertain significance ★ ⚠ same residue
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

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-arg184gly (accessed [today's date]).

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