Is ALG9 p.Met523Val (c.1567A>G) pathogenic?

ALG9 p.Met523Val (c.1567A>G) is classified Likely benign in ALG9 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-06-19). AlphaMissense: ambiguous (0.3607); Rare (popmax 0.228%, sas); Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Met523Val (c.1567A>G)?

ALG9 p.Met523Val (c.1567A>G) is associated with ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Met523Val (c.1567A>G) in the general population?

ALG9 p.Met523Val (c.1567A>G) is rare (popmax 0.228%, sas) (gnomAD).

How is ALG9-CDG inherited?

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

What do computational predictors say about ALG9 p.Met523Val (c.1567A>G)?

AlphaMissense predicts ambiguous (score 0.3607) — an in-silico prediction, not a clinical call.

ALG9 p.Met523Val

c.1567A>G · rs76407349 · VCV2182290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3607 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.228%, sas)

Conditions

ALG9-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.3607	ambiguous
REVEL	0.548	indeterminate
SaProt	LLR -9.96	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.41, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM M516V vs ClinVar M523V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.228% South Asian · 208/91,078 alleles

Filtering AF 0.203% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.193%

Overall 0.0155% 250/1,614,048 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.228%	438
Middle Eastern	0.182%	551
Remaining individualsnot grpmax-eligible	0.024%	4,166
Admixed American	0.00333%	30,007
East Asian	0.00223%	44,888
African / African-American	0.00133%	75,054
European (non-Finnish)	0.00102%	98,326

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.Met523Val
Coding: c.1567A>G
MANE Select: NM_024740
dbSNP: rs76407349
Type: single nucleotide variant
Location: chr11:111836200 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB
Residue 523: a UniProt-annotated variant site (in cdg1l; loss of function in dolichol-linked oligosaccharide biosynthetic process)

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-met523val (accessed [today's date]).

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