Is ALG6 p.Arg18Gln (c.53G>A) pathogenic?

ALG6 p.Arg18Gln (c.53G>A) is classified Conflicting classifications of pathogenicity in ALG6 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-03-10). AlphaMissense: likely pathogenic (0.6194); Very rare (popmax 0.00298%, nfe); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Arg18Gln (c.53G>A)?

ALG6 p.Arg18Gln (c.53G>A) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Arg18Gln (c.53G>A) in the general population?

ALG6 p.Arg18Gln (c.53G>A) is very rare (popmax 0.00298%, nfe) (gnomAD).

How is ALG6-CDG inherited?

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

What do computational predictors say about ALG6 p.Arg18Gln (c.53G>A)?

AlphaMissense predicts likely pathogenic (score 0.6194) — an in-silico prediction, not a clinical call.

ALG6 p.Arg18Gln

c.53G>A · rs1287725303 · VCV552732

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6194 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00298%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG6-congenital disorder of glycosylation 1C

Computational evidence

Protein change
AlphaMissense	0.6194	likely pathogenic
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -10.28	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 66 kb · p 0.00074 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00298% European (non-Finnish) · 35/1,176,182 alleles

Filtering AF 0.00216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00236% 38/1,609,534 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00298%	33,605
Remaining individualsnot grpmax-eligible	0.0016%	62,308
African / African-American	0.00134%	74,772
South Asian	0.0011%	90,972

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.Arg18Gln
Coding: c.53G>A
MANE Select: NM_013339
dbSNP: rs1287725303
Type: single nucleotide variant
Location: chr1:63371030 (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.Arg18= Likely benign ★★ 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-arg18gln (accessed [today's date]).

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