Is CPLANE1 p.Ala2276Pro (c.6825_6826delinsCC) pathogenic?

CPLANE1 p.Ala2276Pro (c.68256826delinsCC) is classified Uncertain significance in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-29). Absent from gnomAD; Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Ala2276Pro (c.6825_6826delinsCC)?

CPLANE1 p.Ala2276Pro (c.6825_6826delinsCC) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Ala2276Pro (c.6825_6826delinsCC) in the general population?

CPLANE1 p.Ala2276Pro (c.6825_6826delinsCC) is absent from gnomAD (gnomAD).

CPLANE1 p.Ala2276Pro

c.6825_6826delinsCC · rs2547570537 · VCV2153056

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Joubert syndrome 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.7	GERP -3.2
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic

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: CPLANE1
Protein: p.Ala2276Pro
Coding: c.6825_6826delinsCC
MANE Select: NM_001384732
dbSNP: rs2547570537
Type: Indel
Location: chr5:37169198 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2276: 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.Glu2776Phe Uncertain significance ★★ same condition
CPLANE1 p.Leu463Pro Uncertain significance ★★ same condition
CPLANE1 p.Gly834fs Likely pathogenic ★ same condition
CPLANE1 p.Ser724fs Likely pathogenic ★ same condition
CPLANE1 p.Glu84Arg Uncertain significance ★ same condition
CPLANE1 p.Phe2033_Thr2034delinsCysMet Uncertain significance ★ same condition
CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2291+1G>A 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-ala2276pro (accessed [today's date]).

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