# NM_001384732.1(CPLANE1):c.3204dup (p.Gln1069fs)

https://sugi.bio/variant/cplane1-p-gln1069fs

## Summary

**CPLANE1 p.Gln1069fs (c.3204dup)** is classified **Pathogenic** in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). Very rare (popmax 0.000174%, nfe).

**At a glance:** Pathogenic · review: Single submitter · rsID rs2150117334 · 1 submitter · very rare (popmax 0.000174%, nfe)

## For patients & families {#patients}

This is a change in the CPLANE1 gene that is reported as disease-causing, but on limited review, submitted by 1 submitter.

*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:** [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.Gln1069fs |
| Coding change (HGVS c.) | c.3204dup |
| MANE Select transcript | [NM_001384732](https://www.ncbi.nlm.nih.gov/nuccore/NM_001384732) |
| dbSNP | [rs2150117334](https://www.ncbi.nlm.nih.gov/snp/rs2150117334/) |
| Variant type | Duplication |
| Location | chr5:37205399-37205400 (GRCh38) |
| ClinVar | [VCV1402222](https://www.ncbi.nlm.nih.gov/clinvar/variation/1402222/) |

**All HGVS expressions:** `NC_000005.10:g.37205404dup`, `NC_000005.9:g.37205506dup`, `NG_032772.2:g.49029dup`, `NM_001384732.1:c.3204dup`, `NM_023073.4:c.3204dup`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **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 7.136, GERP 0.84, phastCons 1 — highly conserved position (PP3-type support)
- 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 18 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 duplication variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.000174%** (nfe) · FAF95 2.9e-05% · FAF99 1.1e-05% · 2/1,146,208 in the highest group · 2/1,398,280 alleles overall — very rare (popmax 0.000174%, nfe).

*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)

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-05-21.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Pathogenic | criteria provided, single submitter | clinical testing | 2024-05-21 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related CPLANE1 variant pages (same residue, condition, or type): [CPLANE1 p.Asn1339Ter](/variant/cplane1-p-asn1339ter), [CPLANE1 p.Asn1865fs](/variant/cplane1-p-asn1865fs), [CPLANE1 p.Asp1467fs](/variant/cplane1-p-asp1467fs), [CPLANE1 p.Cys1277fs](/variant/cplane1-p-cys1277fs), [CPLANE1 p.His3148fs](/variant/cplane1-p-his3148fs), [CPLANE1 p.Ile2119fs](/variant/cplane1-p-ile2119fs), [CPLANE1 p.Ile980fs](/variant/cplane1-p-ile980fs), [CPLANE1 p.Leu1386fs](/variant/cplane1-p-leu1386fs).

### 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 1402222). 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.*