Is ALG9 p.Arg370Ile (c.1109G>T) pathogenic?

ALG9 p.Arg370Ile (c.1109G>T) is classified Uncertain significance in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). AlphaMissense: likely pathogenic (0.9861); Very rare (popmax 8.47e-05%, nfe); Associated with ALG9-associated autosomal dominant polycystic kidney disease.

What condition is associated with ALG9 p.Arg370Ile (c.1109G>T)?

ALG9 p.Arg370Ile (c.1109G>T) is associated with ALG9-associated autosomal dominant polycystic kidney disease (ClinVar).

How common is ALG9 p.Arg370Ile (c.1109G>T) in the general population?

ALG9 p.Arg370Ile (c.1109G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Autosomal dominant polycystic kidney disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ALG9 p.Arg370Ile (c.1109G>T)?

AlphaMissense predicts likely pathogenic (score 0.9861) — an in-silico prediction, not a clinical call.

ALG9 p.Arg370Ile

c.1109G>T · VCV4531711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9861 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG9-associated autosomal dominant polycystic kidney disease

Computational evidence

Protein change
AlphaMissense	0.9861	likely pathogenic · top 8% in ALG9
REVEL	0.974	strongly pathogenic-leaning
SaProt	LLR -15.23	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 6.84e-05% 1/1,461,844 alleles · very rare

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.Arg370Ile
Coding: c.1109G>T
MANE Select: NM_024740
Type: single nucleotide variant
Location: chr11:111840719 (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-associated autosomal dominant polycystic kidney disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant polycystic kidney disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ALG9 p.Arg370Lys Pathogenic same residue
ALG9 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Gln594Ter Uncertain significance ★★ same condition
ALG9 p.Arg407Ter Pathogenic ★ same condition
ALG9 p.Cys71Ter Likely pathogenic ★ same condition
ALG9 p.Gly512Ter Pathogenic ★ same condition
ALG9 p.Arg455Ter Conflicting classifications of pathogenicity ★ same condition
ALG9 p.Arg409fs Pathogenic/Likely pathogenic ★★ 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-arg370ile (accessed [today's date]).

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