Is CPLANE1 p.Ala2425= (c.7275G>A) pathogenic?

CPLANE1 p.Ala2425= (c.7275G>A) is classified Likely benign in CPLANE1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-29). Ultra-rare (popmax 0.0738%, nfe); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Ala2425= (c.7275G>A)?

CPLANE1 p.Ala2425= (c.7275G>A) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Ala2425= (c.7275G>A) in the general population?

CPLANE1 p.Ala2425= (c.7275G>A) is ultra-rare (popmax 0.0738%, nfe) (gnomAD).

CPLANE1 p.Ala2425=

c.7275G>A · rs137899908 · VCV261675

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0738%, nfe)

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 -0.65	GERP -3.5, phastCons 0.044
Overall
CADD	7.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0738% European (non-Finnish) · 871/1,179,738 alleles

Filtering AF 0.0697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0681%

Overall 0.0569% 918/1,612,968 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0738%	1,354
Remaining individualsnot grpmax-eligible	0.0336%	2,974
Middle Eastern	0.0165%	6,050
South Asian	0.0165%	6,053
African / African-American	0.0107%	9,370
East Asian	0.00223%	44,778
Finnishnot grpmax-eligible	0.00156%	63,960

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.Ala2425=
Coding: c.7275G>A
MANE Select: NM_001384732
dbSNP: rs137899908
Type: single nucleotide variant
Location: chr5:37167172 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2425: a UniProt-annotated variant site (in ofd6; likely pathogenic)

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

Also linked: orofaciodigital syndrome type 6

Similar variants

CPLANE1 p.Ala2425Val Uncertain significance ★★ ⚠ 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
CPLANE1 c.3673-1G>C 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-ala2425 (accessed [today's date]).

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