# NM_001777.4(CD47):c.448A>G (p.Ile150Val)

https://sugi.bio/variant/cd47-p-ile150val

## Summary

**CD47 p.Ile150Val (c.448A>G)** is classified **Uncertain significance** in CD47 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-29). AlphaMissense: likely benign (0.068); Very rare (popmax 0.000818%, nfe).

**At a glance:** Uncertain significance · review: Single submitter · 2 submitters · AlphaMissense likely benign · very rare (popmax 0.000818%, nfe)

## For patients & families {#patients}

This is a change in the CD47 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 2 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 | [CD47](https://sugi.bio/atlas/gene/CD47/) |
| Protein change (HGVS p.) | p.Ile150Val |
| Coding change (HGVS c.) | c.448A>G |
| MANE Select transcript | [NM_001777](https://www.ncbi.nlm.nih.gov/nuccore/NM_001777) |
| Variant type | single nucleotide variant |
| Location | chr3:108071135-108071135 (GRCh38) |
| ClinVar | [VCV3264845](https://www.ncbi.nlm.nih.gov/clinvar/variation/3264845/) |

**All HGVS expressions:** `NC_000003.11:g.107789982T>C`, `NC_000003.12:g.108071135T>C`, `NM_001382306.1:c.448A>G`, `NM_001777.4:c.448A>G`, `NM_198793.3:c.448A>G`

## Computational & population evidence {#evidence}

**Concordance:** ClinVar classifies this **uncertain**; the computational predictors unanimously lean **tolerated** — a triage signal, not a reclassification.

- AlphaMissense **likely benign** (0.068)
- REVEL 0.023 (moderately benign-leaning) — agrees with AlphaMissense
- SaProt LLR -5.7 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this tolerated
- SpliceAI predicts **acceptor gain** (Δ 0.44) — a splice-altering prediction on an uncertain variant — a signal for review
- Conservation: phyloP 1.163, GERP -1.37, phastCons 0.998 — weakly conserved position
- CADD: **PHRED 17.89**. 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.*
- Regional missense constraint: **o/e 0.54** across the covering region of the MANE Select transcript (108,059,504–108,080,047), spanning 20,543 bp. Chi-square p 5.3e-07. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI deltas (raw): acceptor loss **0.03**, donor loss **0.00**, acceptor gain **0.44**, donor gain **0.00**. Largest is acceptor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.44**, donor gain **0.00**.
- Pangolin: Δ**0.22** (gain), gain 0.22 / loss 0.05. Agrees with SpliceAI. An independent predictor to SpliceAI — a different model trained on different data. *Descriptive; ClinGen's SVI calibration covers SpliceAI, not Pangolin, so no ACMG code is assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.000818%** (nfe) · FAF95 0.000385% · FAF99 0.000279% · 9/1,099,998 in the highest group · 9/1,506,876 alleles overall — very rare (popmax 0.000818%, nfe).

*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}

**CD47** population constraint: LOEUF 0.725, pLI 0.75934, missense-Z 0.94521. *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 **150** lies in a disulfide bond; an α-helix.

AlphaFold model confidence (whole protein): pLDDT 86.48, 67% of residues very-high.

**15 experimental structure(s)** (PDB): [2JJS](https://www.rcsb.org/structure/2JJS), [2JJT](https://www.rcsb.org/structure/2JJT), [2VSC](https://www.rcsb.org/structure/2VSC), [4CMM](https://www.rcsb.org/structure/4CMM), [4KJY](https://www.rcsb.org/structure/4KJY), [5IWL](https://www.rcsb.org/structure/5IWL) — incl. mutant structure 4KJY.

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

*Describes the biological roles of CD47 (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:** CD47's established molecular role includes fibrinogen binding.


### Pathways affected {#pathways}

CD47 participates in **4 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Cell surface interactions at the vascular wall](https://reactome.org/content/detail/R-HSA-202733) | curated |
| [Integrin cell surface interactions](https://reactome.org/content/detail/R-HSA-216083) | curated |
| [Neutrophil degranulation](https://reactome.org/content/detail/R-HSA-6798695) | curated |
| [Signal regulatory protein family interactions](https://reactome.org/content/detail/R-HSA-391160) | electronic |

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

**Molecular function:** fibrinogen binding, thrombospondin receptor activity, cell-cell adhesion mediator activity.

**Biological process:** positive regulation of cell population proliferation, positive regulation of cell-cell adhesion, regulation of type II interferon production, regulation of interleukin-10 production, regulation of interleukin-12 production, regulation of interleukin-6 production.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-03-29.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

**Submission history:** 2 submissions (2024); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Uncertain significance | criteria provided, single submitter | clinical testing | 2024-03-29 |
| Dr. Peter K. Rogan Lab, Western University |  | no classification provided | in vitro |  |

**Reported phenotype names (ClinVar):** not specified, Colon adenocarcinoma, AllHighlyPenetrant.

## Similar variants {#similar}

Related CD47 variant pages (same residue, condition, or type): [CD47 p.Ala178Gly](/variant/cd47-p-ala178gly), [CD47 p.Ala281Thr](/variant/cd47-p-ala281thr), [CD47 p.Asp104Asn](/variant/cd47-p-asp104asn), [CD47 p.Glu128Lys](/variant/cd47-p-glu128lys), [CD47 p.Gly318Ala](/variant/cd47-p-gly318ala), [CD47 p.Ile127Leu](/variant/cd47-p-ile127leu), [CD47 p.Ile153Val](/variant/cd47-p-ile153val), [CD47 p.Ile195Leu](/variant/cd47-p-ile195leu).

### 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 3264845). 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.*