# NM_018718.3(CEP41):c.162del (p.Asp55fs)

https://sugi.bio/variant/cep41-p-asp55fs

## Summary

**CEP41 p.Asp55fs (c.162del)** is classified **Pathogenic** in CEP41 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). Very rare (popmax 0.000895%, nfe); Associated with Inborn genetic diseases.

**At a glance:** Pathogenic · review: Single submitter · 1 submitter · 1 linked condition · very rare (popmax 0.000895%, nfe)

## For patients & families {#patients}

This is a change in the CEP41 gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to Inborn genetic diseases.

*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 | [CEP41](https://sugi.bio/atlas/gene/CEP41/) |
| Protein change (HGVS p.) | p.Asp55fs |
| Coding change (HGVS c.) | c.162del |
| MANE Select transcript | [NM_018718](https://www.ncbi.nlm.nih.gov/nuccore/NM_018718) |
| Variant type | Deletion |
| Location | chr7:130412224-130412224 (GRCh38) |
| ClinVar | [VCV4839576](https://www.ncbi.nlm.nih.gov/clinvar/variation/4839576/) |

**All HGVS expressions:** `NC_000007.13:g.130052070del`, `NC_000007.14:g.130412229del`, `NG_032164.2:g.33987del`, `NM_001257158.2:c.162del`, `NM_001257159.2:c.114del`, `NM_018718.3:c.162del`, `NR_046443.2:n.212del`

## 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 7.701, GERP 2.33, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 1.066, pLI 0.00023358. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 4 of 11**, 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 (gnomAD v4.1): grpmax **0.000895%** (nfe) · FAF95 0.000453% · FAF99 0.00033% · 10/1,117,362 in the highest group · 10/1,545,008 alleles overall — very rare (popmax 0.000895%, 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}

**CEP41** population constraint: LOEUF 1.066, pLI 0.00023358, missense-Z 0.79493. *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):

- **ciliopathy** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 71.06, 28% of residues very-high.

**1 experimental structure(s)** (PDB): [11YJ](https://www.rcsb.org/structure/11YJ).

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

*Describes the biological roles of CEP41 (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}

CEP41 participates in **7 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [AURKA Activation by TPX2](https://reactome.org/content/detail/R-HSA-8854518) | curated |
| [Anchoring of the basal body to the plasma membrane](https://reactome.org/content/detail/R-HSA-5620912) | curated |
| [Loss of Nlp from mitotic centrosomes](https://reactome.org/content/detail/R-HSA-380259) | curated |
| [Loss of proteins required for interphase microtubule organization from the centrosome](https://reactome.org/content/detail/R-HSA-380284) | curated |
| [Recruitment of NuMA to mitotic centrosomes](https://reactome.org/content/detail/R-HSA-380320) | curated |
| [Recruitment of mitotic centrosome proteins and complexes](https://reactome.org/content/detail/R-HSA-380270) | curated |
| [Regulation of PLK1 Activity at G2/M Transition](https://reactome.org/content/detail/R-HSA-2565942) | curated |

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

**Biological process:** cilium assembly.

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2026-01-26.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Pathogenic | criteria provided, single submitter | clinical testing | 2026-01-26 |

## Associated conditions {#conditions}

[Inborn genetic diseases](https://sugi.bio/atlas/disease/inborn-genetic-diseases/).

**Reported phenotype names (ClinVar):** Inborn genetic diseases.

## Similar variants {#similar}

Related CEP41 variant pages (same residue, condition, or type): [CEP41 p.Asp55Val](/variant/cep41-p-asp55val), [CEP41 p.Asp55=](/variant/cep41-p-asp55), [CEP41 p.Arg286Ter](/variant/cep41-p-arg286ter), [CEP41 p.Ala258Val](/variant/cep41-p-ala258val), [CEP41 p.Ala354Val](/variant/cep41-p-ala354val), [CEP41 p.Arg326Leu](/variant/cep41-p-arg326leu), [CEP41 p.Asn347Ser](/variant/cep41-p-asn347ser), [CEP41 p.Gln185Glu](/variant/cep41-p-gln185glu).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 2026-10-14); 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 4839576). 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.*