Is CPLANE1 p.Cys810Trp (c.2430T>G) pathogenic?

CPLANE1 p.Cys810Trp (c.2430T>G) is classified Uncertain significance in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). AlphaMissense: ambiguous (0.4135); Very rare (popmax 0.000523%, nfe); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Cys810Trp (c.2430T>G)?

CPLANE1 p.Cys810Trp (c.2430T>G) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Cys810Trp (c.2430T>G) in the general population?

CPLANE1 p.Cys810Trp (c.2430T>G) is very rare (popmax 0.000523%, nfe) (gnomAD).

What do computational predictors say about CPLANE1 p.Cys810Trp (c.2430T>G)?

AlphaMissense predicts ambiguous (score 0.4135) — an in-silico prediction, not a clinical call.

CPLANE1 p.Cys810Trp

c.2430T>G · VCV3592524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4135 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000523%, nfe)

Conditions

Joubert syndrome 17

Computational evidence

Protein change
AlphaMissense	0.4135	ambiguous
REVEL	0.145	moderately benign-leaning
Splicing
SpliceAI	Δ0.57	acceptor loss, 10 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.8	GERP -2.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	21.1	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 0.000523% European (non-Finnish) · 6/1,146,834 alleles

Filtering AF 0.000188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000124%

Overall 0.000387% 6/1,551,352 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.Cys810Trp
Coding: c.2430T>G
MANE Select: NM_001384732
Type: single nucleotide variant
Location: chr5:37224602 (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

Similar variants

CPLANE1 p.Cys810Gly Uncertain significance ★★ ⚠ same residue
CPLANE1 p.Cys810Arg 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

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-cys810trp (accessed [today's date]).

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