Is ALG9 p.Arg517Leu (c.1550G>T) pathogenic?

ALG9 p.Arg517Leu (c.1550G>T) is classified Benign in ALG9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-21). AlphaMissense: likely benign (0.2654); Very rare (popmax 0.00017%, nfe); Associated with autosomal dominant polycystic liver disease.

What condition is associated with ALG9 p.Arg517Leu (c.1550G>T)?

ALG9 p.Arg517Leu (c.1550G>T) is associated with autosomal dominant polycystic liver disease (ClinVar).

How common is ALG9 p.Arg517Leu (c.1550G>T) in the general population?

ALG9 p.Arg517Leu (c.1550G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ALG9 p.Arg517Leu (c.1550G>T)?

AlphaMissense predicts likely benign (score 0.2654) — an in-silico prediction, not a clinical call.

ALG9 p.Arg517Leu

c.1550G>T · rs782004306 · VCV638634

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal dominant polycystic liver disease

Computational evidence

Protein change
AlphaMissense	0.2654	likely benign
REVEL	0.462	indeterminate
SaProt	LLR -9.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.64, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R510L vs ClinVar R517L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,930 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,724 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.Arg517Leu
Coding: c.1550G>T
MANE Select: NM_024740
dbSNP: rs782004306
Type: single nucleotide variant
Location: chr11:111836217 (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

autosomal dominant polycystic liver disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG9 p.Arg517Gln Uncertain significance ★★ ⚠ same residue
ALG9 p.Arg517Trp Uncertain significance ★ ⚠ same residue
ALG9 p.Asn315Ser Uncertain significance ★★ ⚠ same condition
ALG9 p.Ala232Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
ALG9 p.Arg370Lys Pathogenic same condition
ALG9 p.Ala280Val Benign ⚠ same condition
ALG9 c.566-1G>A Pathogenic/Likely pathogenic ★★ same type
ALG9 c.896-2A>G Likely pathogenic ★★ 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-arg517leu (accessed [today's date]).

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