Is ALG6 c.987+12A>G pathogenic?

ALG6 c.987+12A>G is classified Benign/Likely benign in ALG6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-21). Rare (popmax 0.212%, amr); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 c.987+12A>G?

ALG6 c.987+12A>G is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 c.987+12A>G in the general population?

ALG6 c.987+12A>G is rare (popmax 0.212%, amr) (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 c.987+12A>G

rs758406155 · VCV389038

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.212%, amr)

Conditions

ALG6-congenital disorder of glycosylation 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -3.1
Non-coding constraint	Z 1.07	1 kb window · o/e 0.91 · regional · uncalibrated
Overall
CADD	9.814	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.212% Admixed American · 127/59,832 alleles

Filtering AF 0.182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.0089% 136/1,528,280 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.212%	471
South Asian	0.00561%	17,840
Remaining individualsnot grpmax-eligible	0.00504%	19,829
European (non-Finnish)	9.07e-05%	1,102,858

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: ALG6
Coding: c.987+12A>G
MANE Select: NM_013339
dbSNP: rs758406155
Type: single nucleotide variant
Location: chr1:63415969 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.08

Full ALG6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG6-congenital disorder of glycosylation 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG6-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG6 c.1128-1G>A Likely pathogenic ★★ same condition
ALG6 c.1128-2A>C Likely pathogenic ★★ same condition
ALG6 c.1326+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.257+5G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.429+1G>T Likely pathogenic ★★ same condition
ALG6 c.495-2A>G Likely pathogenic ★★ same condition
ALG6 c.495-2A>T Likely pathogenic ★★ same condition
ALG6 c.680+1G>A 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/alg6-c-987-plus-12a-g (accessed [today's date]).

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