# NM_001384732.1(CPLANE1):c.6407del (p.Pro2136fs)

https://sugi.bio/variant/cplane1-p-pro2136fs

## Summary

**CPLANE1 p.Pro2136fs (c.6407del)** is classified **Pathogenic** in CPLANE1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2012-04-06). No gnomAD frequency available for this variant; Associated with Joubert syndrome 17.

**At a glance:** Pathogenic · review: No assertion criteria · rsID rs367543064 · 2 submitters · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the CPLANE1 gene that is reported as disease-causing, but on limited review, submitted by 2 submitters, and is linked to Joubert syndrome 17.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0015824/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CPLANE1](https://sugi.bio/atlas/gene/CPLANE1/) |
| Protein change (HGVS p.) | p.Pro2136fs |
| Coding change (HGVS c.) | c.6407del |
| MANE Select transcript | [NM_001384732](https://www.ncbi.nlm.nih.gov/nuccore/NM_001384732) |
| dbSNP | [rs367543064](https://www.ncbi.nlm.nih.gov/snp/rs367543064/) |
| Variant type | Deletion |
| Location | chr5:37170096-37170096 (GRCh38) |
| ClinVar | [VCV31221](https://www.ncbi.nlm.nih.gov/clinvar/variation/31221/) |

**All HGVS expressions:** `NC_000005.10:g.37170098del`, `NC_000005.9:g.37170200del`, `NG_032772.2:g.84333del`, `NM_001384732.1:c.6407del`, `NM_023073.3:c.6407delC`, `NM_023073.4:c.6407del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -0.803, GERP -2.42 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.728, pLI 2.7962e-36. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 33 of 53**, so the transcript is predicted to undergo NMD.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**CPLANE1** population constraint: LOEUF 0.728, pLI 2.7962e-36, missense-Z 2.7342; ClinGen dosage — haploinsufficiency 30, triplosensitivity 0 (0–3 scale). *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **Joubert syndrome 17** — Definitive (AR)

## Protein context {#protein}

Residue **2136** lies in the 'disordered' region.

## Clinical significance {#significance}

**Pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2012-04-06.

**Submitter consensus:** conflicting (1 Pathogenic, 1 not provided).

**Submission history:** 2 submissions (2012); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| OMIM | Pathogenic | no assertion criteria provided | literature only | 2012-04-06 |
| GeneReviews | not provided | no classification provided | literature only |  |

## Associated conditions {#conditions}

[Joubert syndrome 17](https://sugi.bio/atlas/disease/joubert-syndrome-17/).

**Reported phenotype names (ClinVar):** Joubert syndrome 17.

## Similar variants {#similar}

Related CPLANE1 variant pages (same residue, condition, or type): [CPLANE1 p.Asn1182fs](/variant/cplane1-p-asn1182fs), [CPLANE1 p.Gly2717fs](/variant/cplane1-p-gly2717fs), [CPLANE1 p.Ile165fs](/variant/cplane1-p-ile165fs), [CPLANE1 p.Ile1889_Asp1890insTer](/variant/cplane1-p-ile1889-asp1890inster), [CPLANE1 p.Leu465fs](/variant/cplane1-p-leu465fs), [CPLANE1 p.Lys1071fs](/variant/cplane1-p-lys1071fs), [CPLANE1 p.Lys1186fs](/variant/cplane1-p-lys1186fs), [CPLANE1 p.Lys2345fs](/variant/cplane1-p-lys2345fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 31221). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*