Is CPLANE1 p.Ser3052Cys (c.9155C>G) pathogenic?

CPLANE1 p.Ser3052Cys (c.9155C>G) is classified Conflicting classifications of pathogenicity in CPLANE1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0812); Rare (popmax 0.218%, eas); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Ser3052Cys (c.9155C>G)?

CPLANE1 p.Ser3052Cys (c.9155C>G) is associated with Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Ser3052Cys (c.9155C>G) in the general population?

CPLANE1 p.Ser3052Cys (c.9155C>G) is rare (popmax 0.218%, eas) (gnomAD).

What do computational predictors say about CPLANE1 p.Ser3052Cys (c.9155C>G)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

CPLANE1 p.Ser3052Cys

c.9155C>G · rs557372169 · VCV733086

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.218%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Joubert syndrome 17

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.024	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -1.6, phastCons 0.005
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	5.683	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S2998C vs ClinVar S3052C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.218% East Asian · 98/44,878 alleles

Filtering AF 0.183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.17%

Overall 0.0065% 105/1,614,170 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.218%	458
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	8.47e-05%	1,180,018

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.Ser3052Cys
Coding: c.9155C>G
MANE Select: NM_001384732
dbSNP: rs557372169
Type: single nucleotide variant
Location: chr5:37121647 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3052: 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

Similar variants

CPLANE1 p.Ser3052Phe 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-ser3052cys (accessed [today's date]).

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