Is ALG9 p.Arg407Ter (c.1219C>T) pathogenic?

ALG9 p.Arg407Ter (c.1219C>T) is classified Pathogenic in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-26). Very rare (popmax 0.00133%, afr); Associated with ALG9-associated autosomal dominant polycystic kidney disease.

What condition is associated with ALG9 p.Arg407Ter (c.1219C>T)?

ALG9 p.Arg407Ter (c.1219C>T) is associated with ALG9-associated autosomal dominant polycystic kidney disease (ClinVar).

How common is ALG9 p.Arg407Ter (c.1219C>T) in the general population?

ALG9 p.Arg407Ter (c.1219C>T) is very rare (popmax 0.00133%, afr) (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.Arg407Ter

c.1219C>T · VCV4879829

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

ALG9-associated autosomal dominant polycystic kidney disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 15
Splicing
SpliceAI	Δ0.41	acceptor loss, 24 bp away · masked 0 · deltas
Pangolin	Δ0.31	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.1	GERP 0.018, 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 0.00133% African / African-American · 1/74,918 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,613,450 alleles · very rare exomes 7/1,461,288 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,918
European (non-Finnish)	0.000678%	147,436

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.Arg407Ter
Coding: c.1219C>T
MANE Select: NM_024740
Type: single nucleotide variant
Location: chr11:111838354 (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.Cys71Ter Likely 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-arg407ter (accessed [today's date]).

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