Is CPLANE1 p.Pro3102Arg (c.9305C>G) pathogenic?

CPLANE1 p.Pro3102Arg (c.9305C>G) is classified Uncertain significance in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-12). AlphaMissense: likely benign (0.1006); Very rare (popmax 0.00406%, afr); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Pro3102Arg (c.9305C>G)?

CPLANE1 p.Pro3102Arg (c.9305C>G) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Pro3102Arg (c.9305C>G) in the general population?

CPLANE1 p.Pro3102Arg (c.9305C>G) is very rare (popmax 0.00406%, afr) (gnomAD).

What do computational predictors say about CPLANE1 p.Pro3102Arg (c.9305C>G)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

CPLANE1 p.Pro3102Arg

c.9305C>G · VCV3592358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00406%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Joubert syndrome 17

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.011	GERP -2.5
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	8.687	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P3048R vs ClinVar P3102R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00406% African / African-American · 3/73,956 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000499%

Overall 0.000187% 3/1,601,128 alleles · very rare exomes 1/1,449,010 · genomes 2/152,118 · 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.Pro3102Arg
Coding: c.9305C>G
MANE Select: NM_001384732
Type: single nucleotide variant
Location: chr5:37120221 (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.Pro3102Ser Uncertain significance ★★ ⚠ same residue
CPLANE1 p.Pro3102_His3103insProTrpPro 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-pro3102arg (accessed [today's date]).

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