Is CPLANE1 p.Ala2017= (c.6051T>C) pathogenic?

CPLANE1 p.Ala2017= (c.6051T>C) is classified Benign in CPLANE1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 7.62%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Ala2017= (c.6051T>C)?

CPLANE1 p.Ala2017= (c.6051T>C) is associated with Joubert syndrome 17 (ClinVar).

CPLANE1 p.Ala2017=

Q: How common is CPLANE1 p.Ala2017= (c.6051T>C) in the general population?

CPLANE1 p.Ala2017= (c.6051T>C) is common (popmax 7.62%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6051T>C · rs61746147 · VCV158047

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 7.62%, 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 1.1	GERP 1.8, phastCons 1
Overall
CADD	6.505	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.62% African / African-American · 5,714/75,014 alleles

Filtering AF 7.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.38%

Overall 0.395% 6,383/1,614,136 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.62%	13
Remaining individualsnot grpmax-eligible	0.533%	188
Admixed American	0.398%	251
Middle Eastern	0.379%	264
South Asian	0.0274%	3,643
European (non-Finnish)	0.00415%	24,082

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.Ala2017=
Coding: c.6051T>C
MANE Select: NM_001384732
dbSNP: rs61746147
Type: single nucleotide variant
Location: chr5:37173875 (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-ala2017 (accessed [today's date]).

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