Is CPLANE1 p.Cys2138fs (c.6411del) pathogenic?

CPLANE1 p.Cys2138fs (c.6411del) is classified Likely pathogenic in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Cys2138fs (c.6411del)?

CPLANE1 p.Cys2138fs (c.6411del) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

CPLANE1 p.Cys2138fs

c.6411del · VCV3592424

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Joubert syndrome 17

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 33 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.52	GERP -3.4

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

Variant & gene context

Gene: CPLANE1
Protein: p.Cys2138fs
Coding: c.6411del
MANE Select: NM_001384732
Type: Deletion
Location: chr5:37170092 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2138: the 'disordered' region

Full CPLANE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: orofaciodigital syndrome type 6

Similar variants

CPLANE1 p.Asn1182fs Pathogenic ★★ same condition
CPLANE1 p.Gly2717fs Pathogenic ★★ same condition
CPLANE1 p.Ile165fs Pathogenic ★★ same condition
CPLANE1 p.Ile1889_Asp1890insTer Likely pathogenic ★★ same condition
CPLANE1 p.Leu465fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Lys1071fs Likely pathogenic ★★ same condition
CPLANE1 p.Lys1186fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Lys2345fs 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/cplane1-p-cys2138fs (accessed [today's date]).

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