Is ALG5 p.Arg39Ter (c.115C>T) pathogenic?

ALG5 p.Arg39Ter (c.115C>T) is classified Likely pathogenic in ALG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). Very rare (popmax 8.49e-05%, nfe); Associated with polycystic kidney disease 7.

What condition is associated with ALG5 p.Arg39Ter (c.115C>T)?

ALG5 p.Arg39Ter (c.115C>T) is associated with polycystic kidney disease 7 (ClinVar).

How common is ALG5 p.Arg39Ter (c.115C>T) in the general population?

ALG5 p.Arg39Ter (c.115C>T) is very rare (popmax 8.49e-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.

ALG5 p.Arg39Ter

c.115C>T · rs2059045469 · VCV3236195

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 8.49e-05%, nfe)

Conditions

polycystic kidney disease 7

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 10
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.3, phastCons 1
Overall
CADD	38.0	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 8.49e-05% European (non-Finnish) · 1/1,178,456 alleles

Overall 6.88e-05% 1/1,454,346 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: ALG5
Protein: p.Arg39Ter
Coding: c.115C>T
MANE Select: NM_013338
dbSNP: rs2059045469
Type: single nucleotide variant
Location: chr13:36995548 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 92.29

Full ALG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polycystic kidney disease 7 — 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

ALG5 p.Arg39Gln Likely benign ★ same residue
ALG5 p.Thr249Met Uncertain significance ★★ ⚠ same condition
ALG5 c.239-2A>G Likely pathogenic ★ same condition
ALG5 p.Arg97Ter Pathogenic ★ same condition
ALG5 p.Trp224Ter Likely pathogenic ★ same condition
ALG5 p.Arg309Ter Uncertain significance ★ same condition
ALG5 p.Gln235His Uncertain significance ★ ⚠ same condition
ALG5 p.Gln235Leu 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/alg5-p-arg39ter (accessed [today's date]).

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