# NM_177965.4(CFAP418):c.89_99del (p.Pro30fs)

https://sugi.bio/variant/cfap418-p-pro30fs

## Summary

**CFAP418 p.Pro30fs (c.89_99del)** is classified **Pathogenic** in CFAP418 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-17). No gnomAD frequency available for this variant.

**At a glance:** Pathogenic · review: Single submitter · rsID rs2132171444 · 1 submitter · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the CFAP418 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 | [CFAP418](https://sugi.bio/atlas/gene/CFAP418/) |
| Protein change (HGVS p.) | p.Pro30fs |
| Coding change (HGVS c.) | c.89_99del |
| MANE Select transcript | [NM_177965](https://www.ncbi.nlm.nih.gov/nuccore/NM_177965) |
| dbSNP | [rs2132171444](https://www.ncbi.nlm.nih.gov/snp/rs2132171444/) |
| Variant type | Deletion |
| Location | chr8:95269091-95269101 (GRCh38) |
| ClinVar | [VCV1681151](https://www.ncbi.nlm.nih.gov/clinvar/variation/1681151/) |

**All HGVS expressions:** `NC_000008.10:g.96281321_96281331del`, `NC_000008.11:g.95269093_95269103del`, `NG_032804.1:g.5134_5144del`, `NM_001363260.1:c.89_99del`, `NM_177965.4:c.89_99del`

## 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 -0.29, GERP -0.682 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 1.642, pLI 1.7648e-05. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 1 of 6**, 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}

**CFAP418** population constraint: LOEUF 1.642, pLI 1.7648e-05, missense-Z 0.13822; 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):

- **ciliopathy** — Definitive (AR)

## Protein context {#protein}

Residue **30** lies in the 'required for interaction with fam161a' region; the 'disordered' region.

AlphaFold model confidence (whole protein): pLDDT 75.73, 42% of residues very-high.

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-10-17.

**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 | 2022-10-17 |

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

## Similar variants {#similar}

Related CFAP418 variant pages (same residue, condition, or type): [CFAP418 p.Pro30Ala](/variant/cfap418-p-pro30ala), [CFAP418 p.Glu60fs](/variant/cfap418-p-glu60fs), [CFAP418 c.375-10del](/variant/cfap418-c-375-minus-10del), [CFAP418 p.Arg42fs](/variant/cfap418-p-arg42fs), [CFAP418 p.Asn121fs](/variant/cfap418-p-asn121fs), [CFAP418 p.Asp6fs](/variant/cfap418-p-asp6fs), [CFAP418 p.Glu162fs](/variant/cfap418-p-glu162fs), [CFAP418 p.Gly117fs](/variant/cfap418-p-gly117fs).

### 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 1681151). 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.*