Is CPLANE1 p.Ile1358= (c.4074C>T) pathogenic?

CPLANE1 p.Ile1358= (c.4074C>T) is classified Conflicting classifications of pathogenicity in CPLANE1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-02). Rare (popmax 0.298%, mid); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Ile1358= (c.4074C>T)?

CPLANE1 p.Ile1358= (c.4074C>T) is associated with Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Ile1358= (c.4074C>T) in the general population?

CPLANE1 p.Ile1358= (c.4074C>T) is rare (popmax 0.298%, mid) (gnomAD).

CPLANE1 p.Ile1358=

c.4074C>T · rs145018253 · VCV771563

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.298%, 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 1.6	GERP -2.3, phastCons 1
Overall
CADD	7.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.298% Middle Eastern · 18/6,038 alleles

Filtering AF 0.193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.159%

Overall 0.0322% 518/1,609,578 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.298%	335
South Asian	0.039%	2,567
European (non-Finnish)	0.0362%	2,760
Remaining individualsnot grpmax-eligible	0.0289%	3,464
African / African-American	0.0147%	6,799
Admixed American	0.0118%	8,441
East Asian	0.00223%	44,822
Finnishnot grpmax-eligible	0.00156%	63,966

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.Ile1358=
Coding: c.4074C>T
MANE Select: NM_001384732
dbSNP: rs145018253
Type: single nucleotide variant
Location: chr5:37187420 (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

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

Similar variants

CPLANE1 p.Ile1358Met Uncertain significance ★ ⚠ same residue
CPLANE1 p.Ile1358Val 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

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-ile1358 (accessed [today's date]).

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