Is ALG5 p.Arg309Ter (c.925C>T) pathogenic?

ALG5 p.Arg309Ter (c.925C>T) is classified Uncertain significance in ALG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). Very rare (popmax 0.0011%, sas); Associated with polycystic kidney disease 7.

What condition is associated with ALG5 p.Arg309Ter (c.925C>T)?

ALG5 p.Arg309Ter (c.925C>T) is associated with polycystic kidney disease 7 (ClinVar).

How common is ALG5 p.Arg309Ter (c.925C>T) in the general population?

ALG5 p.Arg309Ter (c.925C>T) is very rare (popmax 0.0011%, sas) (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.Arg309Ter

c.925C>T · VCV3907697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, 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

Grpmax group 0.0011% South Asian · 1/90,928 alleles

Overall 0.000205% 3/1,461,064 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,448
South Asiangrpmax	0.0011%	90,928
European (non-Finnish)	8.48e-05%	1,179,778

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg309Ter
Coding: c.925C>T
MANE Select: NM_013338
Type: single nucleotide variant
Location: chr13:36949992 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 92.29
Residue 309: a UniProt-annotated variant site (in pkd7)

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.Arg309Gln Uncertain significance ★ ⚠ same residue
ALG5 p.Arg309Leu Uncertain significance ★ ⚠ same residue
ALG5 p.Thr249Met Uncertain significance ★★ ⚠ same condition
ALG5 c.239-2A>G Likely pathogenic ★ same condition
ALG5 p.Arg39Ter Likely pathogenic ★ same condition
ALG5 p.Arg97Ter Pathogenic ★ same condition
ALG5 p.Trp224Ter Likely pathogenic ★ same condition
ALG5 p.Gln235His 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-arg309ter (accessed [today's date]).

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