Is SEC63 p.Asp596fs (c.1786_1787del) pathogenic?

SEC63 p.Asp596fs (c.17861787del) is classified Likely pathogenic in SEC63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-21). Associated with polycystic liver disease 2.

What condition is associated with SEC63 p.Asp596fs (c.1786_1787del)?

SEC63 p.Asp596fs (c.1786_1787del) is associated with polycystic liver disease 2, biliary tract disorder (ClinVar).

SEC63 p.Asp596fs

c.1786_1787del · VCV3592889

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

polycystic liver disease 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 17 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -3.4, phastCons 0.2

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

Variant & gene context

Gene: SEC63
Protein: p.Asp596fs
Coding: c.1786_1787del
MANE Select: NM_007214
Type: Microsatellite
Location: chr6:107883034 (GRCh38)
Gene constraint: LOEUF 0.532 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.71
Residue 596: the 'disordered' region; a UniProt-annotated variant site (in pcld2)

Full SEC63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polycystic liver disease 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: biliary tract disorder

Similar variants

SEC63 p.Phe16del Uncertain significance ★★ same condition
SEC63 c.125_126del Likely pathogenic ★ same condition
SEC63 p.Tyr444fs Pathogenic ★ same condition
SEC63 p.Glu568del Conflicting classifications of pathogenicity ★ same condition
SEC63 p.Glu580del Uncertain significance ★ same condition
SEC63 c.452+1G>A Pathogenic/Likely pathogenic ★★ same condition
SEC63 c.625-2A>G Likely pathogenic ★★ same condition
SEC63 c.733+1G>A 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/sec63-p-asp596fs (accessed [today's date]).

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