Is CPLANE1 p.Ala1783Asp (c.5348C>A) pathogenic?

CPLANE1 p.Ala1783Asp (c.5348C>A) is classified Pathogenic/Likely pathogenic in CPLANE1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-06-02). AlphaMissense: likely pathogenic (0.9208); Very rare (popmax 0.00271%, nfe); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Ala1783Asp (c.5348C>A)?

CPLANE1 p.Ala1783Asp (c.5348C>A) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6, Joubert syndrome and related disorders (ClinVar).

How common is CPLANE1 p.Ala1783Asp (c.5348C>A) in the general population?

CPLANE1 p.Ala1783Asp (c.5348C>A) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about CPLANE1 p.Ala1783Asp (c.5348C>A)?

AlphaMissense predicts likely pathogenic (score 0.9208) — an in-silico prediction, not a clinical call.

CPLANE1 p.Ala1783Asp

c.5348C>A · rs200444162 · VCV427895

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely pathogenic

0.9208 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Joubert syndrome 17

Computational evidence

Protein change
AlphaMissense	0.9208	likely pathogenic ✓ concordant with ClinVar · top 2% in CPLANE1
REVEL	0.731	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% European (non-Finnish) · 32/1,179,860 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00198% 32/1,613,470 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.Ala1783Asp
Coding: c.5348C>A
MANE Select: NM_001384732
dbSNP: rs200444162
Type: single nucleotide variant
Location: chr5:37182833 (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

Also linked: orofaciodigital syndrome type 6 Joubert syndrome and related disorders

Similar variants

CPLANE1 p.Ala1783= Likely benign ★ 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-ala1783asp (accessed [today's date]).

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