Is ALG12 p.Pro155= (c.465T>C) pathogenic?

ALG12 p.Pro155= (c.465T>C) is classified Benign in ALG12 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-22). Rare (popmax 0.168%, amr); Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 p.Pro155= (c.465T>C)?

ALG12 p.Pro155= (c.465T>C) is associated with ALG12-congenital disorder of glycosylation (ClinVar).

How common is ALG12 p.Pro155= (c.465T>C) in the general population?

ALG12 p.Pro155= (c.465T>C) is rare (popmax 0.168%, amr) (gnomAD).

How is ALG12-CDG inherited?

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

ALG12 p.Pro155=

c.465T>C · rs201564211 · VCV786788

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.168%, amr)

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	<0.2	all four deltas below 0.2 · A>C here scores Δ0.83 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.7	GERP -2.8
Overall
CADD	0.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.168% Admixed American · 101/60,014 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.00657% 106/1,613,364 alleles · rare exomes 101/1,461,034 · genomes 5/152,330 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.168%	594
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000339%	294,977

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.Pro155=
Coding: c.465T>C
MANE Select: NM_024105
dbSNP: rs201564211
Type: single nucleotide variant
Location: chr22:49910438 (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-pro155 (accessed [today's date]).

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