Is ALG8 p.Arg364Gln (c.1091G>A) pathogenic?

ALG8 p.Arg364Gln (c.1091G>A) is classified Uncertain significance in ALG8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-23). AlphaMissense: likely benign (0.0931); Ultra-rare (popmax 0.0164%, mid); Associated with polycystic liver disease 3 with or without kidney cysts.

How common is ALG8 p.Arg364Gln (c.1091G>A) in the general population?

ALG8 p.Arg364Gln (c.1091G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ALG8 p.Arg364Gln (c.1091G>A)?

AlphaMissense predicts likely benign (score 0.0931) — an in-silico prediction, not a clinical call.

ALG8 p.Arg364Gln

Q: What condition is associated with ALG8 p.Arg364Gln (c.1091G>A)?

ALG8 p.Arg364Gln (c.1091G>A) is associated with polycystic liver disease 3 with or without kidney cysts, ALG8-congenital disorder of glycosylation (ClinVar).

c.1091G>A · rs766238263 · VCV883482

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0931 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

polycystic liver disease 3 with or without kidney cysts

Computational evidence

Protein change
AlphaMissense	0.0931	likely benign
REVEL	0.449	indeterminate
SaProt	LLR -6.65	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 1.1	GERP 2.1, phastCons 0.52
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00533% 86/1,613,922 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.00686%	14,568
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00134%	74,894

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: ALG8
Protein: p.Arg364Gln
Coding: c.1091G>A
MANE Select: NM_024079
dbSNP: rs766238263
Type: single nucleotide variant
Location: chr11:78106894 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 364: a UniProt-annotated variant site (in pcld3)

Full ALG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polycystic liver disease 3 with or without kidney cysts — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG8-congenital disorder of glycosylation

Similar variants

ALG8 p.Arg364Ter Pathogenic/Likely pathogenic ★★ same residue
ALG8 c.368+2T>G Likely pathogenic ★★ same condition
ALG8 c.674-2A>G Likely pathogenic ★★ same condition
ALG8 c.777+1G>A Likely pathogenic ★★ same condition
ALG8 c.95+1G>A Likely pathogenic ★★ same condition
ALG8 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Arg268Ter Pathogenic/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/alg8-p-arg364gln (accessed [today's date]).

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