Is ALG8 p.Leu241fs (c.710_719dup) pathogenic?

ALG8 p.Leu241fs (c.710719dup) is classified Likely pathogenic in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). Absent from gnomAD; Associated with polycystic liver disease 3 with or without kidney cysts.

What condition is associated with ALG8 p.Leu241fs (c.710_719dup)?

ALG8 p.Leu241fs (c.710_719dup) is associated with polycystic liver disease 3 with or without kidney cysts (ClinVar).

How common is ALG8 p.Leu241fs (c.710_719dup) in the general population?

ALG8 p.Leu241fs (c.710_719dup) is absent from gnomAD (gnomAD).

ALG8 p.Leu241fs

c.710_719dup · rs2136903056 · VCV1333512

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

polycystic liver disease 3 with or without kidney cysts

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP -1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALG8
Protein: p.Leu241fs
Coding: c.710_719dup
MANE Select: NM_024079
dbSNP: rs2136903056
Type: Duplication
Location: chr11:78113943 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 241: 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

Similar variants

ALG8 p.Leu104fs Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Pro255fs Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Ser372fs Likely pathogenic ★★ same condition
ALG8 p.Val328fs Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Ile46fs Likely pathogenic ★ same condition
ALG8 p.Trp55fs Likely pathogenic ★ same condition
ALG8 c.368+2T>G Likely pathogenic ★★ same condition
ALG8 c.674-2A>G 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-leu241fs (accessed [today's date]).

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