# NM_016122.3(CEP83):c.1323G>A (p.Arg441=)

https://sugi.bio/variant/cep83-p-arg441

## Summary

**CEP83 p.Arg441= (c.1323G>A)** is classified **Likely benign** in CEP83 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). Ultra-rare (popmax 0.0101%, amr); Associated with nephronophthisis 18.

**At a glance:** Likely benign · review: Single submitter · rsID rs1202585370 · 1 submitter · 1 linked condition · ultra-rare (popmax 0.0101%, amr)

## For patients & families {#patients}

This is a change in the CEP83 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter, and is linked to nephronophthisis 18.

*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.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |
| Age of onset (of this condition) | Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal |
| Prevalence | 1-9 / 100 000 (Finland) |
| Diagnostic panels | CEP83 is a diagnostic-grade gene on 14 Genomics England panels |

**Commonly reported features of Nephronophthisis** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Renal insufficiency — Frequent (79-30%)
- Anemia — Frequent (79-30%)
- Abnormality of retinal pigmentation — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0024992/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CEP83](https://sugi.bio/atlas/gene/CEP83/) |
| Protein change (HGVS p.) | p.Arg441= |
| Coding change (HGVS c.) | c.1323G>A |
| MANE Select transcript | [NM_016122](https://www.ncbi.nlm.nih.gov/nuccore/NM_016122) |
| dbSNP | [rs1202585370](https://www.ncbi.nlm.nih.gov/snp/rs1202585370/) |
| Variant type | single nucleotide variant |
| Location | chr12:94367814-94367814 (GRCh38) |
| ClinVar | [VCV1629898](https://www.ncbi.nlm.nih.gov/clinvar/variation/1629898/) |

**All HGVS expressions:** `NC_000012.11:g.94761590C>T`, `NC_000012.12:g.94367814C>T`, `NG_051825.1:g.97175G>A`, `NM_001042399.2:c.1323G>A`, `NM_001346457.2:c.1323G>A`, `NM_001346458.2:c.1011G>A`, `NM_001346459.2:c.1011G>A`, `NM_001368037.1:c.1323G>A`, `NM_001368038.1:c.1323G>A`, `NM_001368039.1:c.1011G>A`, `NM_001368040.1:c.1011G>A`, `NM_001368041.1:c.1098G>A`, `NM_016122.3:c.1323G>A`, `NR_160432.1:n.2076G>A`

## 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 -0.586, GERP -4.81, phastCons 0.049 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 1.574**. 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: **below the reporting threshold**. This position is scored for a different substitution (C>A, Δ0.98 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.0101%** (amr) · FAF95 0.0043% · FAF99 0.00296% · 6/59,700 in the highest group · 7/1,611,948 alleles overall — ultra-rare (popmax 0.0101%, amr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Admixed American (grpmax) | 0.0101% | 9,950 |
| Finnish (not grpmax-eligible) | 0.00158% | 63,460 |

*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}

**CEP83** population constraint: LOEUF 0.807, pLI 1.2207e-05, missense-Z 1.02. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 81.90, 50% of residues very-high.

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

*Describes the biological roles of CEP83 (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}

CEP83 participates in **1 Reactome pathway** (⚕ = disease pathway):

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

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

**Biological process:** obsolete vesicle docking, cilium assembly, protein localization to centrosome.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-04-17.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2025-04-17 |

## Associated conditions {#conditions}

[nephronophthisis 18](https://sugi.bio/atlas/disease/nephronophthisis-18/).

**Reported phenotype names (ClinVar):** Nephronophthisis 18.

## Similar variants {#similar}

Related CEP83 variant pages (same residue, condition, or type): [CEP83 p.Arg441Gly](/variant/cep83-p-arg441gly), [CEP83 p.Arg209Ter](/variant/cep83-p-arg209ter), [CEP83 p.Arg215Ter](/variant/cep83-p-arg215ter), [CEP83 p.Arg511Pro](/variant/cep83-p-arg511pro), [CEP83 p.Arg511Ter](/variant/cep83-p-arg511ter), [CEP83 p.Gln81Ter](/variant/cep83-p-gln81ter), [CEP83 p.Leu351Ter](/variant/cep83-p-leu351ter), [CEP83 p.Ala232Val](/variant/cep83-p-ala232val).

### 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 1629898). 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.*