Is CPLANE1 p.Arg978Ter (c.2932C>T) pathogenic?

CPLANE1 p.Arg978Ter (c.2932C>T) is classified Pathogenic in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-06). Very rare (popmax 0.00244%, eas); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Arg978Ter (c.2932C>T)?

CPLANE1 p.Arg978Ter (c.2932C>T) is associated with Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Arg978Ter (c.2932C>T) in the general population?

CPLANE1 p.Arg978Ter (c.2932C>T) is very rare (popmax 0.00244%, eas) (gnomAD).

CPLANE1 p.Arg978Ter

c.2932C>T · rs1359437084 · VCV846826

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Conditions

Joubert syndrome 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 53
Splicing
SpliceAI	Δ0.30	acceptor loss · deltas
Pangolin	Δ0.40	loss · gain 0.11 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.4	GERP 0.17, phastCons 1
Overall
CADD	36.0	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 0.00244% East Asian · 1/40,914 alleles

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

Overall 0.000286% 4/1,397,156 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00244%	40,914
South Asian	0.00119%	84,004
European (non-Finnish)	0.000175%	572,466

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.Arg978Ter
Coding: c.2932C>T
MANE Select: NM_001384732
dbSNP: rs1359437084
Type: single nucleotide variant
Location: chr5:37206414 (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.Arg978Gln Uncertain significance ★★ same residue
CPLANE1 p.Arg978= Likely benign ★ 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-arg978ter (accessed [today's date]).

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