Is ALG9 p.Ala232Pro (c.694G>C) pathogenic?

ALG9 p.Ala232Pro (c.694G>C) is classified Conflicting classifications of pathogenicity in ALG9 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2024-03-06). AlphaMissense: likely pathogenic (0.8071); Ultra-rare (popmax 0.099%, mid); Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Ala232Pro (c.694G>C)?

ALG9 p.Ala232Pro (c.694G>C) is associated with ALG9-congenital disorder of glycosylation, autosomal dominant polycystic liver disease, Gillessen-Kaesbach-Nishimura syndrome (ClinVar).

How common is ALG9 p.Ala232Pro (c.694G>C) in the general population?

ALG9 p.Ala232Pro (c.694G>C) is ultra-rare (popmax 0.099%, mid) (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.Ala232Pro (c.694G>C)?

AlphaMissense predicts likely pathogenic (score 0.8071) — an in-silico prediction, not a clinical call.

ALG9 p.Ala232Pro

c.694G>C · rs36111204 · VCV96135

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8071 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ALG9-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.8071	likely pathogenic
REVEL	0.395	indeterminate
SaProt	LLR -15.25	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 27 kb · p 0.019 · regional, not allelic
Overall
CADD	27.4	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 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.0528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0514%

Overall 0.0445% 718/1,614,126 alleles · ultra-rare exomes 666/1,461,844 · genomes 52/152,282 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
European (non-Finnish)	0.0564%	1,774
Finnishnot grpmax-eligible	0.0359%	2,784
Remaining individualsnot grpmax-eligible	0.0192%	5,208
Admixed American	0.00667%	15,002
African / African-American	0.00533%	18,760
South Asian	0.00439%	22,772

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.Ala232Pro
Coding: c.694G>C
MANE Select: NM_024740
dbSNP: rs36111204
Type: single nucleotide variant
Location: chr11:111857609 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB
Residue 232: 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

Also linked: autosomal dominant polycystic liver disease Gillessen-Kaesbach-Nishimura syndrome

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-ala232pro (accessed [today's date]).

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