Is ALG12 p.Pro385= (c.1155C>T) pathogenic?

ALG12 p.Pro385= (c.1155C>T) is classified Conflicting classifications of pathogenicity in ALG12 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-03-01). Rare (popmax 0.957%, afr); Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 p.Pro385= (c.1155C>T)?

ALG12 p.Pro385= (c.1155C>T) is associated with ALG12-congenital disorder of glycosylation (ClinVar).

How common is ALG12 p.Pro385= (c.1155C>T) in the general population?

ALG12 p.Pro385= (c.1155C>T) is rare (popmax 0.957%, afr) (gnomAD).

How is ALG12-CDG inherited?

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

ALG12 p.Pro385=

c.1155C>T · rs113652023 · VCV96094

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.957%, afr)

Conditions

ALG12-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.055	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.08	GERP -3
Overall
CADD	5.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.957% African / African-American · 718/75,050 alleles

Filtering AF 0.899% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.876%

Overall 0.0512% 826/1,614,192 alleles · rare exomes 434/1,461,876 · genomes 392/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.957%	105
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Admixed American	0.0583%	1,715
South Asian	0.00549%	18,217
European (non-Finnish)	0.000847%	118,003

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.Pro385=
Coding: c.1155C>T
MANE Select: NM_024105
dbSNP: rs113652023
Type: single nucleotide variant
Location: chr22:49904344 (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

ZBED4 p.Ser385Leu 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
ALG12 c.469+5G>A 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-pro385 (accessed [today's date]).

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