Is CPLANE1 p.Lys1071fs (c.3213del) pathogenic?

CPLANE1 p.Lys1071fs (c.3213del) is classified Likely pathogenic in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-30). Very rare (popmax 0.000174%, nfe); Associated with orofaciodigital syndrome type 6.

What condition is associated with CPLANE1 p.Lys1071fs (c.3213del)?

CPLANE1 p.Lys1071fs (c.3213del) is associated with orofaciodigital syndrome type 6, Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Lys1071fs (c.3213del) in the general population?

CPLANE1 p.Lys1071fs (c.3213del) is very rare (popmax 0.000174%, nfe) (gnomAD).

CPLANE1 p.Lys1071fs

c.3213del · VCV3592507

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Conditions

orofaciodigital syndrome type 6

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 18 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -2, phastCons 1
Overall
CADD	23.4	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 0.000174% European (non-Finnish) · 2/1,146,452 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000129% 2/1,550,606 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.Lys1071fs
Coding: c.3213del
MANE Select: NM_001384732
Type: Deletion
Location: chr5:37205391 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Disease context

orofaciodigital syndrome type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 17

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.Lys1186fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Lys2345fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Lys303fs 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-lys1071fs (accessed [today's date]).

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