Is ALG9 p.Tyr598His (c.1792T>C) pathogenic?

ALG9 p.Tyr598His (c.1792T>C) is classified Conflicting classifications of pathogenicity in ALG9 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-08-20). AlphaMissense: likely benign (0.2341); Rare (popmax 0.44%, afr); Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Tyr598His (c.1792T>C)?

ALG9 p.Tyr598His (c.1792T>C) is associated with ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Tyr598His (c.1792T>C) in the general population?

ALG9 p.Tyr598His (c.1792T>C) is rare (popmax 0.44%, afr) (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.Tyr598His (c.1792T>C)?

AlphaMissense predicts likely benign (score 0.2341) — an in-silico prediction, not a clinical call.

ALG9 p.Tyr598His

c.1792T>C · rs201194863 · VCV704070

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2341 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.44%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG9-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.2341	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -11.00	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.37	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	24.5	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 Y591H vs ClinVar Y598H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.44% African / African-American · 330/75,016 alleles

Filtering AF 0.401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.385%

Overall 0.0222% 358/1,614,128 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.44%	227
Remaining individualsnot grpmax-eligible	0.0272%	3,677
Middle Eastern	0.0165%	6,060
Admixed American	0.0133%	7,502
European (non-Finnish)	0.000169%	590,005

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.Tyr598His
Coding: c.1792T>C
MANE Select: NM_024740
dbSNP: rs201194863
Type: single nucleotide variant
Location: chr11:111786462 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB

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.Tyr598= 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-tyr598his (accessed [today's date]).

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