Is CPLANE1 p.Tyr3013= (c.9039T>C) pathogenic?

CPLANE1 p.Tyr3013= (c.9039T>C) is classified Conflicting classifications of pathogenicity in CPLANE1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-14). Ultra-rare (popmax 0.0164%, mid); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Tyr3013= (c.9039T>C)?

CPLANE1 p.Tyr3013= (c.9039T>C) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Tyr3013= (c.9039T>C) in the general population?

CPLANE1 p.Tyr3013= (c.9039T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CPLANE1 p.Tyr3013=

c.9039T>C · rs1030945020 · VCV2202303

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.48	GERP -2.8
Overall
CADD	0.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000372% 6/1,613,856 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.00333%	29,997
African / African-American	0.00133%	74,926
South Asian	0.0011%	91,068
European (non-Finnish)	8.48e-05%	1,179,870

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.Tyr3013=
Coding: c.9039T>C
MANE Select: NM_001384732
dbSNP: rs1030945020
Type: single nucleotide variant
Location: chr5:37121763 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3013: a UniProt-annotated variant site (in ofd6; likely pathogenic); 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.Tyr3013Cys Uncertain significance ★★ ⚠ same residue
CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2291+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2291+2T>C Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2292-1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2500+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.3290-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.3673-1G>C 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-tyr3013 (accessed [today's date]).

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