Is CPLANE1 p.Lys1807= (c.5421G>A) pathogenic?

CPLANE1 p.Lys1807= (c.5421G>A) is classified Conflicting classifications of pathogenicity in CPLANE1 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.64%, mid); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Lys1807= (c.5421G>A)?

CPLANE1 p.Lys1807= (c.5421G>A) is associated with Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Lys1807= (c.5421G>A) in the general population?

CPLANE1 p.Lys1807= (c.5421G>A) is low-frequency (popmax 1.64%, mid) (gnomAD).

CPLANE1 p.Lys1807=

c.5421G>A · rs149313666 · VCV158041

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.64%, mid)

Conditions

Joubert syndrome 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.36	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.3	GERP -0.52, phastCons 1
Overall
CADD	12.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.64% Middle Eastern · 98/5,964 alleles

Filtering AF 1.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3%

Overall 0.638% 10,099/1,582,064 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.4%	29
Ashkenazi Jewishnot grpmax-eligible	1.97%	51
Middle Easterngrpmax	1.64%	61
South Asian	1.39%	72
Remaining individualsnot grpmax-eligible	0.72%	139
European (non-Finnish)	0.616%	162
Finnishnot grpmax-eligible	0.506%	198
Admixed American	0.373%	268
African / African-American	0.081%	1,234

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys1807=
Coding: c.5421G>A
MANE Select: NM_001384732
dbSNP: rs149313666
Type: single nucleotide variant
Location: chr5:37182760 (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 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
CPLANE1 c.677+1G>C 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-lys1807 (accessed [today's date]).

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