Is ALG12 p.Ala295= (c.885A>G) pathogenic?

ALG12 p.Ala295= (c.885A>G) is classified Benign in ALG12 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 74%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 p.Ala295= (c.885A>G)?

ALG12 p.Ala295= (c.885A>G) is associated with ALG12-congenital disorder of glycosylation (ClinVar).

How is ALG12-CDG inherited?

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

ALG12 p.Ala295=

Q: How common is ALG12 p.Ala295= (c.885A>G) in the general population?

ALG12 p.Ala295= (c.885A>G) is common (popmax 74%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.885A>G · rs8135963 · VCV96102

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 74%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

ALG12-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.002	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.2
Overall
CADD	0.161	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 74% African / African-American · 55,461/74,954 alleles

Filtering AF 73.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 73.3%

Overall 24.1% 388,741/1,613,820 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	74%	1
Amishnot grpmax-eligible	46.8%	2
South Asian	42.4%	2
Middle Eastern	32.5%	3
Ashkenazi Jewishnot grpmax-eligible	29.8%	3
Remaining individualsnot grpmax-eligible	25.8%	4
European (non-Finnish)	20.3%	5
Admixed American	17.6%	6
Finnishnot grpmax-eligible	16.8%	6
East Asian	13.9%	7

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.Ala295=
Coding: c.885A>G
MANE Select: NM_024105
dbSNP: rs8135963
Type: single nucleotide variant
Location: chr22:49907828 (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-ala295 (accessed [today's date]).

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