Is ALG9 p.Arg584Trp (c.1750C>T) pathogenic?

ALG9 p.Arg584Trp (c.1750C>T) is classified Conflicting classifications of pathogenicity in ALG9 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-01). AlphaMissense: likely pathogenic (0.872); Very rare (popmax 0.00492%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG9 p.Arg584Trp (c.1750C>T)?

ALG9 p.Arg584Trp (c.1750C>T) is associated with Inborn genetic diseases, ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Arg584Trp (c.1750C>T) in the general population?

ALG9 p.Arg584Trp (c.1750C>T) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about ALG9 p.Arg584Trp (c.1750C>T)?

AlphaMissense predicts likely pathogenic (score 0.872) — an in-silico prediction, not a clinical call.

ALG9 p.Arg584Trp

c.1750C>T · rs199995104 · VCV703589

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.872 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.872	likely pathogenic
REVEL	0.864	moderately pathogenic-leaning
SaProt	LLR -15.55	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 5.2	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	29.6	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 R577W vs ClinVar R584W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00492% European (non-Finnish) · 58/1,179,932 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.0251% 405/1,613,824 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.01%	99
Remaining individualsnot grpmax-eligible	0.0704%	1,420
European (non-Finnish)grpmax	0.00492%	20,344
African / African-American	0.00267%	37,442
South Asian	0.0022%	45,536

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg584Trp
Coding: c.1750C>T
MANE Select: NM_024740
dbSNP: rs199995104
Type: single nucleotide variant
Location: chr11:111786504 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG9-congenital disorder of glycosylation

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-arg584trp (accessed [today's date]).

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