# NM_001164496.2(CFAP44):c.3645G>A (p.Lys1215=)

https://sugi.bio/variant/cfap44-p-lys1215

## Summary

**CFAP44 p.Lys1215= (c.3645G>A)** is classified **Likely benign** in CFAP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-06). Very rare (popmax 0.00541%, nfe).

**At a glance:** Likely benign · review: Single submitter · rsID rs761359904 · 1 submitter · very rare (popmax 0.00541%, nfe)

## For patients & families {#patients}

This is a change in the CFAP44 gene that is classified as likely benign — not considered disease-causing, 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 | [CFAP44](https://sugi.bio/atlas/gene/CFAP44/) |
| Protein change (HGVS p.) | p.Lys1215= |
| Coding change (HGVS c.) | c.3645G>A |
| MANE Select transcript | [NM_001164496](https://www.ncbi.nlm.nih.gov/nuccore/NM_001164496) |
| dbSNP | [rs761359904](https://www.ncbi.nlm.nih.gov/snp/rs761359904/) |
| Variant type | single nucleotide variant |
| Location | chr3:113330639-113330639 (GRCh38) |
| ClinVar | [VCV796322](https://www.ncbi.nlm.nih.gov/clinvar/variation/796322/) |

**All HGVS expressions:** `NC_000003.11:g.113049486C>T`, `NC_000003.12:g.113330639C>T`, `NM_001164496.2:c.3645G>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 0.778, GERP -3.94, phastCons 0.999 — weakly conserved position
- CADD: **PHRED 5.158**. 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, Δ0.28 acceptor 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 **0.00541%** (nfe) · FAF95 0.00431% · FAF99 0.00391% · 62/1,146,338 in the highest group · 64/1,535,314 alleles overall — very rare (popmax 0.00541%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| European (non-Finnish) (grpmax) | 0.00541% | 18,489 |
| Remaining individuals (not grpmax-eligible) | 0.00333% | 30,009 |

*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}

**CFAP44** population constraint: LOEUF 0.697, pLI 1.5316e-20, missense-Z 1.8195. *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 **1215** lies in a UniProt-annotated variant site (in spgf20).

AlphaFold model confidence (whole protein): pLDDT 74.87, 27% of residues very-high.

**1 experimental structure(s)** (PDB): [8J07](https://www.rcsb.org/structure/8J07).

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

*Describes the biological roles of CFAP44 (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.*

**How this variant is thought to act:** CFAP44's established molecular role includes peptidase activity.


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

**Molecular function:** peptidase activity.

**Biological process:** microtubule cytoskeleton organization, sperm axoneme assembly.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2018-12-06.

**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 | 2018-12-06 |

**Reported phenotype names (ClinVar):** not provided, none provided, RECLASSIFIED - ADRA2C POLYMORPHISM, RECLASSIFIED - ADRB1 POLYMORPHISM.

## Similar variants {#similar}

Related CFAP44 variant pages (same residue, condition, or type): [CFAP44 p.Glu463Ter](/variant/cfap44-p-glu463ter), [CFAP44 c.4759-3C>T](/variant/cfap44-c-4759-minus-3c-t), [CFAP44 p.Ala157=](/variant/cfap44-p-ala157), [CFAP44 p.Ala486Val](/variant/cfap44-p-ala486val), [CFAP44 p.Arg1059Gln](/variant/cfap44-p-arg1059gln), [CFAP44 p.Arg1495Trp](/variant/cfap44-p-arg1495trp), [CFAP44 p.Arg1651Trp](/variant/cfap44-p-arg1651trp), [CFAP44 p.Arg1806=](/variant/cfap44-p-arg1806).

### 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 796322). 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.*