# NM_012072.4(CD93):c.1449GGA[1] (p.Glu484del)

https://sugi.bio/variant/cd93-p-glu484del

## Summary

**CD93 p.Glu484del (c.1449GGA[1])** is classified **Likely benign** in CD93 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-27). Rare (popmax 0.2%, mid); Associated with CD93-related disorder.

**At a glance:** Likely benign · review: No assertion criteria · rsID rs556056799 · 1 submitter · 1 linked condition · rare (popmax 0.2%, mid)

## For patients & families {#patients}

This is a change in the CD93 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter, and is linked to CD93-related disorder.

*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 | [CD93](https://sugi.bio/atlas/gene/CD93/) |
| Protein change (HGVS p.) | p.Glu484del |
| Coding change (HGVS c.) | c.1449GGA[1] |
| MANE Select transcript | [NM_012072](https://www.ncbi.nlm.nih.gov/nuccore/NM_012072) |
| dbSNP | [rs556056799](https://www.ncbi.nlm.nih.gov/snp/rs556056799/) |
| Variant type | Microsatellite |
| Location | chr20:23084739-23084741 (GRCh38) |
| ClinVar | [VCV3044385](https://www.ncbi.nlm.nih.gov/clinvar/variation/3044385/) |

**All HGVS expressions:** `NC_000020.10:g.23065378CTC[1]`, `NC_000020.11:g.23084741CTC[1]`, `NM_012072.4:c.1449GGA[1]`

## 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 -0.528, GERP -3.44 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- Molecular consequence: **in-frame indel**.
- CADD: **PHRED 0.74**. 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 assessed** — the release is built from a substitutions-only source, so it holds no microsatellite 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 **0.2%** (mid) · FAF95 0.126% · FAF99 0.116% · 12/6,004 in the highest group · 536/1,607,004 alleles overall — rare (popmax 0.2%, mid).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Middle Eastern (grpmax) | 0.2% | 500 |
| Admixed American | 0.151% | 662 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.0967% | 1,034 |
| Remaining individuals (not grpmax-eligible) | 0.0676% | 1,479 |
| South Asian | 0.0365% | 2,736 |
| European (non-Finnish) | 0.0275% | 3,633 |
| African / African-American | 0.00937% | 10,673 |
| Finnish (not grpmax-eligible) | 0.00159% | 63,054 |

*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}

**CD93** population constraint: LOEUF 1.237, pLI 1.2172e-14, missense-Z -0.76676. *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 **484** lies in the 'disordered' region.

AlphaFold model confidence (whole protein): pLDDT 73.07, 30% of residues very-high.

**2 experimental structure(s)** (PDB): [8A59](https://www.rcsb.org/structure/8A59), [8IVD](https://www.rcsb.org/structure/8IVD).

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

*Describes the biological roles of CD93 (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:** CD93's established molecular role includes complement component C1q complex binding. p.Glu484del falls in the disordered region.


### Pathways affected {#pathways}

CD93 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Neutrophil degranulation](https://reactome.org/content/detail/R-HSA-6798695) | curated |

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

**Molecular function:** complement component C1q complex binding, signaling receptor activity.

**Biological process:** angiogenesis, cell-cell adhesion.

## Clinical significance {#significance}

**Likely benign** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2023-11-27.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2023-11-27 |

## Associated conditions {#conditions}

[CD93-related disorder](https://sugi.bio/atlas/disease/cd93-related-disorder/).

**Reported phenotype names (ClinVar):** CD93-related disorder, CD93-related condition.

## Similar variants {#similar}

Related CD93 variant pages (same residue, condition, or type): [CD93 p.Arg634Ter](/variant/cd93-p-arg634ter), [CD93 p.Met187Ile](/variant/cd93-p-met187ile), [CD93 p.Arg496Cys](/variant/cd93-p-arg496cys), [CD93 p.Arg496His](/variant/cd93-p-arg496his), [CD93 p.Ser41=](/variant/cd93-p-ser41), [CD93 p.Val117Gly](/variant/cd93-p-val117gly), [CD93 p.Leu15del](/variant/cd93-p-leu15del).

### 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 3044385). 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.*