Is ALG9 p.Arg370Lys (c.1109G>A) pathogenic?

ALG9 p.Arg370Lys (c.1109G>A) is classified Pathogenic in ALG9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-17). AlphaMissense: likely pathogenic (0.9643); Absent from gnomAD v4.1; Associated with polycystic kidney disease 1.

What condition is associated with ALG9 p.Arg370Lys (c.1109G>A)?

ALG9 p.Arg370Lys (c.1109G>A) is associated with polycystic kidney disease 1, autosomal dominant polycystic liver disease (ClinVar).

How common is ALG9 p.Arg370Lys (c.1109G>A) in the general population?

ALG9 p.Arg370Lys (c.1109G>A) is absent from gnomAD v4.1 (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.Arg370Lys (c.1109G>A)?

AlphaMissense predicts likely pathogenic (score 0.9643) — an in-silico prediction, not a clinical call.

ALG9 p.Arg370Lys

c.1109G>A · rs782464678 · VCV631493

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9643 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

polycystic kidney disease 1

Computational evidence

Protein change
AlphaMissense	0.9643	likely pathogenic ✓ concordant with ClinVar
REVEL	0.912	moderately pathogenic-leaning
SaProt	LLR -13.04	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	28.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALG9
Protein: p.Arg370Lys
Coding: c.1109G>A
MANE Select: NM_024740
dbSNP: rs782464678
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

polycystic kidney disease 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant polycystic liver disease

For Autosomal dominant polycystic kidney disease (Orphanet):

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

Similar variants

ALG9 p.Arg370Ile Uncertain significance ★ ⚠ same residue
ALG9 p.Asn315Ser Uncertain significance ★★ ⚠ same condition
ALG9 p.Ala232Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
ALG9 p.Trp227Ter Pathogenic same condition
ALG9 p.Ala280Val Benign ⚠ same condition
ALG9 p.Arg517Leu Benign ⚠ same condition
ALG9 c.566-1G>A Pathogenic/Likely pathogenic ★★ same type
ALG9 c.896-2A>G Likely pathogenic ★★ same type

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-arg370lys (accessed [today's date]).

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