Is ALG9 p.Arg7= (c.21G>C) pathogenic?

ALG9 p.Arg7= (c.21G>C) is classified Likely benign in ALG9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-20). Ultra-rare (popmax 0.041%, afr); Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Arg7= (c.21G>C)?

ALG9 p.Arg7= (c.21G>C) is associated with ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Arg7= (c.21G>C) in the general population?

ALG9 p.Arg7= (c.21G>C) is ultra-rare (popmax 0.041%, afr) (gnomAD).

How is ALG9-CDG inherited?

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

ALG9 p.Arg7=

c.21G>C · VCV4683692

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.041%, afr)

Conditions

ALG9-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP -2.9, phastCons 1
Overall
CADD	11.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.041% African / African-American · 30/73,160 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0255%

Overall 0.00202% 31/1,536,758 alleles · ultra-rare exomes 20/1,384,416 · genomes 11/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.041%	2,439
Remaining individualsnot grpmax-eligible	0.00167%	60,002

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: ALG9
Protein: p.Arg7=
Coding: c.21G>C
MANE Select: NM_024740
Type: single nucleotide variant
Location: chr11:111871462 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB
Residue 7: the 'disordered' region

Full ALG9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG9-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG9-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ALG9 c.566-1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG9 c.896-2A>G Likely pathogenic ★★ same condition
ALG9 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Trp248Ter Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Tyr287Cys Pathogenic/Likely pathogenic ★★ same condition
ALG9 c.*1607C>T Uncertain significance ★★ same condition
ALG9 c.*1624A>C Uncertain significance ★★ same condition
ALG9 c.*1722C>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/alg9-p-arg7 (accessed [today's date]).

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