Is CPLANE1 p.Ser243Arg (c.729T>A) pathogenic?

CPLANE1 p.Ser243Arg (c.729T>A) is classified Uncertain significance in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.1919); Very rare (popmax 0.000963%, nfe); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Ser243Arg (c.729T>A)?

CPLANE1 p.Ser243Arg (c.729T>A) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Ser243Arg (c.729T>A) in the general population?

CPLANE1 p.Ser243Arg (c.729T>A) is very rare (popmax 0.000963%, nfe) (gnomAD).

What do computational predictors say about CPLANE1 p.Ser243Arg (c.729T>A)?

AlphaMissense predicts likely benign (score 0.1919) — an in-silico prediction, not a clinical call.

CPLANE1 p.Ser243Arg

c.729T>A · VCV3592573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000963%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Joubert syndrome 17

Computational evidence

Protein change
AlphaMissense	0.1919	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP 1.7, phastCons 0.39
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	12.47	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000963% European (non-Finnish) · 11/1,142,240 alleles

Filtering AF 0.000517% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000378%

Overall 0.000713% 11/1,543,616 alleles · very rare exomes 11/1,391,314 · genomes 0/152,302 · joint denominator

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.Ser243Arg
Coding: c.729T>A
MANE Select: NM_001384732
Type: single nucleotide variant
Location: chr5:37239818 (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 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-ser243arg (accessed [today's date]).

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