Is ALG9 p.Trp227Ter (c.681G>A) pathogenic?

ALG9 p.Trp227Ter (c.681G>A) is classified Pathogenic in ALG9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-20). Absent from gnomAD v4.1; Associated with polycystic kidney disease 1.

What condition is associated with ALG9 p.Trp227Ter (c.681G>A)?

ALG9 p.Trp227Ter (c.681G>A) is associated with polycystic kidney disease 1 (ClinVar).

How common is ALG9 p.Trp227Ter (c.681G>A) in the general population?

ALG9 p.Trp227Ter (c.681G>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.

ALG9 p.Trp227Ter

c.681G>A · rs1592341222 · VCV631494

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

polycystic kidney disease 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Trp227Ter
Coding: c.681G>A
MANE Select: NM_024740
dbSNP: rs1592341222
Type: single nucleotide variant
Location: chr11:111857622 (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

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 condition
ALG9 c.566-1G>A Pathogenic/Likely pathogenic ★★ same type
ALG9 c.896-2A>G Likely pathogenic ★★ same type
ALG9 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same type
ALG9 p.Trp248Ter Pathogenic/Likely pathogenic ★★ same type
ALG9 p.Tyr287Cys Pathogenic/Likely pathogenic ★★ same type
ALG9 c.*1607C>T Uncertain significance ★★ same type
ALG9 c.*1624A>C Uncertain significance ★★ 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-trp227ter (accessed [today's date]).

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