Is ALG6 p.Arg18= (c.54A>G) pathogenic?

ALG6 p.Arg18= (c.54A>G) is classified Likely benign in ALG6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-22). Rare (popmax 0.133%, sas); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Arg18= (c.54A>G)?

ALG6 p.Arg18= (c.54A>G) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Arg18= (c.54A>G) in the general population?

ALG6 p.Arg18= (c.54A>G) is rare (popmax 0.133%, sas) (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 p.Arg18=

c.54A>G · rs373800951 · VCV755501

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.133%, sas)

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
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.33	GERP -4.6, phastCons 0.97
Overall
CADD	8.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.133% South Asian · 121/90,976 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.00826% 133/1,609,632 alleles · rare exomes 125/1,457,482 · genomes 8/152,150 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.133%	752
Remaining individualsnot grpmax-eligible	0.00321%	31,164
European (non-Finnish)	0.00085%	117,614

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
Protein: p.Arg18=
Coding: c.54A>G
MANE Select: NM_013339
dbSNP: rs373800951
Type: single nucleotide variant
Location: chr1:63371031 (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 p.Arg18Ter Pathogenic/Likely pathogenic ★★ same residue
ALG6 p.Arg18Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-p-arg18 (accessed [today's date]).

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