Is CPLANE1 p.Ser3053fs (c.9157del) pathogenic?

CPLANE1 p.Ser3053fs (c.9157del) is classified Likely pathogenic in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). Very rare (popmax 0.00534%, afr); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Ser3053fs (c.9157del)?

CPLANE1 p.Ser3053fs (c.9157del) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Ser3053fs (c.9157del) in the general population?

CPLANE1 p.Ser3053fs (c.9157del) is very rare (popmax 0.00534%, afr) (gnomAD).

CPLANE1 p.Ser3053fs

c.9157del · VCV3592362

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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 49 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.014	GERP -1.5
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,916 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,038 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: CPLANE1
Protein: p.Ser3053fs
Coding: c.9157del
MANE Select: NM_001384732
Type: Deletion
Location: chr5:37121645 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3053: a UniProt-annotated variant site (in ofd6; likely pathogenic)

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-ser3053fs (accessed [today's date]).

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