Is ALG9 p.Ser255= (c.765G>A) pathogenic?

ALG9 p.Ser255= (c.765G>A) is classified Likely benign in ALG9 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-13). Very rare (popmax 0.00814%, nfe); Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Ser255= (c.765G>A)?

ALG9 p.Ser255= (c.765G>A) is associated with ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Ser255= (c.765G>A) in the general population?

ALG9 p.Ser255= (c.765G>A) is very rare (popmax 0.00814%, nfe) (gnomAD).

How is ALG9-CDG inherited?

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

ALG9 p.Ser255=

c.765G>A · rs372338362 · VCV512394

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00814%, nfe)

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 -10	GERP -3.7
Overall
CADD	0.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00814% European (non-Finnish) · 96/1,180,004 alleles

Filtering AF 0.00681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00601% 97/1,613,956 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00814%	12,292
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Ser255=
Coding: c.765G>A
MANE Select: NM_024740
dbSNP: rs372338362
Type: single nucleotide variant
Location: chr11:111853673 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB
Residue 255: a UniProt-annotated variant site (in)

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 p.Ser255Leu Benign/Likely benign ★★ ⚠ same residue
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

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-ser255 (accessed [today's date]).

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