# NM_024548.4(CEP97):c.2206del (p.Ser736fs)

https://sugi.bio/variant/cep97-p-ser736fs

## Summary

**CEP97 p.Ser736fs (c.2206del)** is classified **Uncertain significance** in CEP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-11). Very rare (popmax 0.000678%, nfe).

**At a glance:** Uncertain significance · review: Single submitter · rsID rs758638500 · 1 submitter · very rare (popmax 0.000678%, nfe)

## For patients & families {#patients}

This is a change in the CEP97 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, 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 | [CEP97](https://sugi.bio/atlas/gene/CEP97/) |
| Protein change (HGVS p.) | p.Ser736fs |
| Coding change (HGVS c.) | c.2206del |
| MANE Select transcript | [NM_024548](https://www.ncbi.nlm.nih.gov/nuccore/NM_024548) |
| dbSNP | [rs758638500](https://www.ncbi.nlm.nih.gov/snp/rs758638500/) |
| Variant type | Deletion |
| Location | chr3:101765158-101765158 (GRCh38) |
| ClinVar | [VCV1962138](https://www.ncbi.nlm.nih.gov/clinvar/variation/1962138/) |

**All HGVS expressions:** `NC_000003.11:g.101484003del`, `NC_000003.12:g.101765159del`, `NM_001303401.2:c.2029del`, `NM_001410784.1:c.2104delT`, `NM_001410785.1:c.1927delT`, `NM_024548.4:c.2206del`

## 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 11.214, GERP 1.85, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.847, pLI 1.4351e-07. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in the last exon (11 of 11)** — predicted to **escape NMD**, so the truncated protein is likely expressed. An input to PVS1, not an applied code.
- CADD: **PHRED 28.3**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- 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 (gnomAD v4.1): grpmax **0.000678%** (nfe) · FAF95 0.000292% · FAF99 0.000211% · 8/1,180,052 in the highest group · 8/1,614,130 alleles overall — very rare (popmax 0.000678%, 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}

**CEP97** population constraint: LOEUF 0.847, pLI 1.4351e-07, missense-Z 1.397. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **736** lies in the 'ccp110-binding' region; the 'interaction with mphosph9' region; the 'disordered' region.

AlphaFold model confidence (whole protein): pLDDT 58.89, 23% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of CEP97 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*


### Pathways affected {#pathways}

CEP97 participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Anchoring of the basal body to the plasma membrane](https://reactome.org/content/detail/R-HSA-5620912) | curated |
| [RHOV GTPase cycle](https://reactome.org/content/detail/R-HSA-9013424) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Biological process:** regulation of mitotic spindle assembly, negative regulation of cilium assembly.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-08-11.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Uncertain significance | criteria provided, single submitter | clinical testing | 2023-08-11 |

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

## Similar variants {#similar}

Related CEP97 variant pages (same residue, condition, or type): [CEP97 p.Ser736=](/variant/cep97-p-ser736), [CEP97 p.Ala36fs](/variant/cep97-p-ala36fs), [CEP97 p.Ile174fs](/variant/cep97-p-ile174fs), [CEP97 p.Ile238fs](/variant/cep97-p-ile238fs), [CEP97 p.Ile604_Arg605delinsMet](/variant/cep97-p-ile604-arg605delinsmet), [CEP97 p.Leu718fs](/variant/cep97-p-leu718fs), [CEP97 p.Ser723fs](/variant/cep97-p-ser723fs), [CEP97 c.447+14_447+17del](/variant/cep97-c-447-plus-14-447-plus-17del).

### 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 1962138). 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.*