Is ALG9 p.Arg607Trp (c.1819C>T) pathogenic?

ALG9 p.Arg607Trp (c.1819C>T) is classified Uncertain significance in ALG9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-31). AlphaMissense: likely benign (0.2019); Ultra-rare (popmax 0.0117%, amr); Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Arg607Trp (c.1819C>T)?

ALG9 p.Arg607Trp (c.1819C>T) is associated with ALG9-congenital disorder of glycosylation, Gillessen-Kaesbach-Nishimura syndrome (ClinVar).

How common is ALG9 p.Arg607Trp (c.1819C>T) in the general population?

ALG9 p.Arg607Trp (c.1819C>T) is ultra-rare (popmax 0.0117%, amr) (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.Arg607Trp (c.1819C>T)?

AlphaMissense predicts likely benign (score 0.2019) — an in-silico prediction, not a clinical call.

ALG9 p.Arg607Trp

c.1819C>T · rs781849410 · VCV3111433

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2019 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG9-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.2019	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -12.48	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	27.9	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 R600W vs ClinVar R607W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,972 alleles

Filtering AF 0.00708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0066%

Overall 0.00719% 116/1,613,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,567
European (non-Finnish)	0.00847%	11,800
African / African-American	0.00668%	14,977
East Asian	0.00223%	44,886
South Asian	0.0022%	45,539
Finnishnot grpmax-eligible	0.00156%	64,014

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.Arg607Trp
Coding: c.1819C>T
MANE Select: NM_024740
dbSNP: rs781849410
Type: single nucleotide variant
Location: chr11:111786435 (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

Also linked: Gillessen-Kaesbach-Nishimura syndrome

For ALG9-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ALG9 p.Arg607Gln Uncertain significance ★★ ⚠ 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-arg607trp (accessed [today's date]).

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