Is CPLANE1 p.Leu171fs (c.510dup) pathogenic?

CPLANE1 p.Leu171fs (c.510dup) is classified Pathogenic in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-02-23). Very rare (popmax 0.00137%, afr); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Leu171fs (c.510dup)?

CPLANE1 p.Leu171fs (c.510dup) is associated with Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Leu171fs (c.510dup) in the general population?

CPLANE1 p.Leu171fs (c.510dup) is very rare (popmax 0.00137%, afr) (gnomAD).

CPLANE1 p.Leu171fs

c.510dup · rs779680371 · VCV217576

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Conditions

Joubert syndrome 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -0.48, phastCons 0.12
Overall
CADD	22.8	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 0.00137% African / African-American · 1/72,934 alleles

Overall 0.000659% 1/151,848 alleles · very rare

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.Leu171fs
Coding: c.510dup
MANE Select: NM_001384732
dbSNP: rs779680371
Type: Duplication
Location: chr5:37244434 (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.Asn1339Ter Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Asp1467fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Cys1277fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.His3148fs Likely pathogenic ★★ same condition
CPLANE1 p.Ile2119fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Ile980fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Leu1386fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Met1958fs 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-leu171fs (accessed [today's date]).

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