Is CPLANE1 p.Pro1378= (c.4134T>C) pathogenic?

CPLANE1 p.Pro1378= (c.4134T>C) is classified Benign/Likely benign in CPLANE1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.02%, afr); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Pro1378= (c.4134T>C)?

CPLANE1 p.Pro1378= (c.4134T>C) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Pro1378= (c.4134T>C) in the general population?

CPLANE1 p.Pro1378= (c.4134T>C) is low-frequency (popmax 2.02%, afr) (gnomAD).

CPLANE1 p.Pro1378=

c.4134T>C · rs79935028 · VCV158035

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.02%, afr)

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 0.85	GERP -3.6, phastCons 0.98
Overall
CADD	3.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.02% African / African-American · 1,514/74,924 alleles

Filtering AF 1.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9%

Overall 0.107% 1,720/1,607,824 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.02%	49
Admixed American	0.157%	638
Remaining individualsnot grpmax-eligible	0.14%	716
Middle Eastern	0.0991%	1,009
South Asian	0.0022%	45,420
European (non-Finnish)	0.00145%	69,088

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.Pro1378=
Coding: c.4134T>C
MANE Select: NM_001384732
dbSNP: rs79935028
Type: single nucleotide variant
Location: chr5:37186341 (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

Also linked: orofaciodigital syndrome type 6

Similar variants

CPLANE1 p.Pro1378Ser 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-pro1378 (accessed [today's date]).

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