Is ALG9 p.Val289Ile (c.865G>A) pathogenic?

ALG9 p.Val289Ile (c.865G>A) is classified Benign in ALG9 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0869); Common (popmax 58.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Gillessen-Kaesbach-Nishimura syndrome.

What condition is associated with ALG9 p.Val289Ile (c.865G>A)?

ALG9 p.Val289Ile (c.865G>A) is associated with Gillessen-Kaesbach-Nishimura syndrome, ALG9-congenital disorder of glycosylation (ClinVar).

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.Val289Ile (c.865G>A)?

AlphaMissense predicts likely benign (score 0.0869) — an in-silico prediction, not a clinical call.

ALG9 p.Val289Ile

Q: How common is ALG9 p.Val289Ile (c.865G>A) in the general population?

ALG9 p.Val289Ile (c.865G>A) is common (popmax 58.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.865G>A · rs10502151 · VCV379945

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0869 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 58.6%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Gillessen-Kaesbach-Nishimura syndrome

Computational evidence

Protein change
AlphaMissense	0.0869	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -10.27	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	GERP 0.83, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 27 kb · p 0.019 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 58.6% East Asian · 26,273/44,852 alleles

Filtering AF 58% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.7%

Overall 33.7% 543,760/1,612,176 alleles · common exomes 499,046/1,460,124 · genomes 44,714/152,052 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	58.6%	2
Amishnot grpmax-eligible	55.3%	2
South Asian	38.6%	3
Finnishnot grpmax-eligible	38.2%	3
Admixed American	37%	3
Middle Eastern	34.8%	3
European (non-Finnish)	33.5%	3
Remaining individualsnot grpmax-eligible	33.2%	3
Ashkenazi Jewishnot grpmax-eligible	26.3%	4
African / African-American	13.9%	7

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.Val289Ile
Coding: c.865G>A
MANE Select: NM_024740
dbSNP: rs10502151
Type: single nucleotide variant
Location: chr11:111853410 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB
Residue 289: a UniProt-annotated variant site (in)

Full ALG9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Gillessen-Kaesbach-Nishimura syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG9-congenital disorder of glycosylation

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-val289ile (accessed [today's date]).

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