# NM_194302.4(CFAP65):c.5442C>T (p.Ile1814=)

https://sugi.bio/variant/cfap65-p-ile1814

## Summary

**CFAP65 p.Ile1814= (c.5442C>T)** is classified **Benign/Likely benign** in CFAP65 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-04). Low-frequency (popmax 1.36%, afr).

**At a glance:** Benign/Likely benign · review: Multiple submitters · rsID rs139829270 · 3 submitters · low-frequency (popmax 1.36%, afr)

## For patients & families {#patients}

This is a change in the CFAP65 gene that is classified as benign/likely benign — not considered disease-causing, submitted by 3 submitters.

*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 | [CFAP65](https://sugi.bio/atlas/gene/CFAP65/) |
| Protein change (HGVS p.) | p.Ile1814= |
| Coding change (HGVS c.) | c.5442C>T |
| dbSNP | [rs139829270](https://www.ncbi.nlm.nih.gov/snp/rs139829270/) |
| Variant type | single nucleotide variant |
| Location | chr2:219004065-219004065 (GRCh38) |
| ClinVar | [VCV775818](https://www.ncbi.nlm.nih.gov/clinvar/variation/775818/) |

**All HGVS expressions:** `NC_000002.11:g.219868787G>A`, `NC_000002.12:g.219004065G>A`, `NG_051336.1:g.42487C>T`, `NM_194302.4:c.5442C>T`

## 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 -4.972, GERP -3.09 — fast-evolving / accelerated position
- CADD: **PHRED 0.049**. 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 looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **1.36%** (afr) · FAF95 1.29% · FAF99 1.27% · 1,022/75,012 in the highest group · 1,137/1,613,976 alleles overall — low-frequency (popmax 1.36%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 1.36% | 73 |
| Remaining individuals (not grpmax-eligible) | 0.08% | 1,250 |
| Admixed American | 0.0783% | 1,277 |
| Middle Eastern | 0.033% | 3,031 |
| East Asian | 0.00669% | 14,959 |
| South Asian | 0.00329% | 30,357 |
| Finnish (not grpmax-eligible) | 0.00156% | 63,914 |
| European (non-Finnish) | 0.000763% | 131,112 |

*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.*

## Clinical significance {#significance}

**Benign/Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2024-11-04.

**Submitter consensus:** conflicting (2 Benign, 1 Likely benign).

**Submission history:** 3 submissions (2018–2024); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2018-11-15 |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |
| Blueprint Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2024-11-04 |

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

### 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 775818). 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.*