Is ALG9 p.Cys71Ter (c.213T>A) pathogenic?

ALG9 p.Cys71Ter (c.213T>A) is classified Likely pathogenic in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Very rare (popmax 8.48e-05%, nfe); Associated with ALG9-associated autosomal dominant polycystic kidney disease.

What condition is associated with ALG9 p.Cys71Ter (c.213T>A)?

ALG9 p.Cys71Ter (c.213T>A) is associated with ALG9-associated autosomal dominant polycystic kidney disease (ClinVar).

How common is ALG9 p.Cys71Ter (c.213T>A) in the general population?

ALG9 p.Cys71Ter (c.213T>A) is very rare (popmax 8.48e-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.

ALG9 p.Cys71Ter

c.213T>A · VCV4531721

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

ALG9-associated autosomal dominant polycystic kidney disease

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 2 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -5.4, phastCons 1
Overall
CADD	33.0	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,552 alleles

Overall 6.84e-05% 1/1,461,078 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.Cys71Ter
Coding: c.213T>A
MANE Select: NM_024740
Type: single nucleotide variant
Location: chr11:111870289 (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.Arg143Ter Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Gln594Ter Uncertain significance ★★ same condition
ALG9 p.Arg407Ter Pathogenic ★ same condition
ALG9 p.Gly512Ter Pathogenic ★ same condition
ALG9 p.Arg370Ile Uncertain significance ★ ⚠ same condition
ALG9 p.Arg455Ter Conflicting classifications of pathogenicity ★ same condition
ALG9 p.Arg409fs Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Ala175fs 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-cys71ter (accessed [today's date]).

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