Is ALG12 p.Ala213= (c.639C>T) pathogenic?

ALG12 p.Ala213= (c.639C>T) is classified Conflicting classifications of pathogenicity in ALG12 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-16). Rare (popmax 0.332%, eas); Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 p.Ala213= (c.639C>T)?

ALG12 p.Ala213= (c.639C>T) is associated with ALG12-congenital disorder of glycosylation (ClinVar).

How common is ALG12 p.Ala213= (c.639C>T) in the general population?

ALG12 p.Ala213= (c.639C>T) is rare (popmax 0.332%, eas) (gnomAD).

How is ALG12-CDG inherited?

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

ALG12 p.Ala213=

c.639C>T · rs140835842 · VCV342050

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.332%, eas)

Conditions

ALG12-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -3.1
Overall
CADD	0.353	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.332% East Asian · 149/44,886 alleles

Filtering AF 0.288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.272%

Overall 0.00997% 161/1,614,136 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.332%	301
Remaining individualsnot grpmax-eligible	0.0064%	15,626
Admixed American	0.00333%	30,016
South Asian	0.0022%	45,542
European (non-Finnish)	0.000339%	295,006

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.Ala213=
Coding: c.639C>T
MANE Select: NM_024105
dbSNP: rs140835842
Type: single nucleotide variant
Location: chr22:49909919 (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-p-ala213 (accessed [today's date]).

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