Is CPLANE1 p.Ala1080= (c.3240C>T) pathogenic?

CPLANE1 p.Ala1080= (c.3240C>T) is classified Benign/Likely benign in CPLANE1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-28). Common (popmax 5.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Ala1080= (c.3240C>T)?

CPLANE1 p.Ala1080= (c.3240C>T) is associated with Joubert syndrome 17 (ClinVar).

CPLANE1 p.Ala1080=

Q: How common is CPLANE1 p.Ala1080= (c.3240C>T) in the general population?

CPLANE1 p.Ala1080= (c.3240C>T) is common (popmax 5.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3240C>T · rs28514632 · VCV158030

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 5.1%, afr) — too common for a highly-penetrant pathogenic allele

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 0.66	GERP 0.89, phastCons 1
Overall
CADD	7.913	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.1% African / African-American · 3,725/73,006 alleles

Filtering AF 4.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.91%

Overall 0.283% 4,393/1,550,770 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.1%	20
Middle Eastern	0.434%	230
Remaining individualsnot grpmax-eligible	0.398%	251
Admixed American	0.354%	283
Ashkenazi Jewishnot grpmax-eligible	0.0349%	2,864
South Asian	0.025%	3,997
European (non-Finnish)	0.0167%	5,972

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.Ala1080=
Coding: c.3240C>T
MANE Select: NM_001384732
dbSNP: rs28514632
Type: single nucleotide variant
Location: chr5:37205364 (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-ala1080 (accessed [today's date]).

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