# NM_001774.3(CD37):c.132G>C (p.Val44=)

https://sugi.bio/variant/cd37-p-val44

## Summary

**CD37 p.Val44= (c.132G>C)** is classified **Benign** in CD37 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-29). Low-frequency (popmax 4.92%, eas).

**At a glance:** Benign · review: Multiple submitters · rsID rs75218499 · 2 submitters · low-frequency (popmax 4.92%, eas)

## For patients & families {#patients}

This is a change in the CD37 gene that is classified as benign — not considered disease-causing, 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 | [CD37](https://sugi.bio/atlas/gene/CD37/) |
| Protein change (HGVS p.) | p.Val44= |
| Coding change (HGVS c.) | c.132G>C |
| MANE Select transcript | [NM_001774](https://www.ncbi.nlm.nih.gov/nuccore/NM_001774) |
| dbSNP | [rs75218499](https://www.ncbi.nlm.nih.gov/snp/rs75218499/) |
| Variant type | single nucleotide variant |
| Location | chr19:49335776-49335776 (GRCh38) |
| ClinVar | [VCV789460](https://www.ncbi.nlm.nih.gov/clinvar/variation/789460/) |

**All HGVS expressions:** `NC_000019.10:g.49335776G>C`, `NC_000019.9:g.49839033G>C`, `NG_033941.1:g.5357G>C`, `NM_001040031.2:c.-73G>C`, `NM_001774.3:c.132G>C`

## 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 5.322, GERP 4.77, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 12.76**. 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 (G>A, Δ0.93 donor 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 **4.92%** (eas) · FAF95 4.75% · FAF99 4.68% · 2,208/44,858 in the highest group · 3,097/1,612,720 alleles overall — low-frequency (popmax 4.92%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| East Asian (grpmax) | 4.92% | 20 |
| South Asian | 0.622% | 161 |
| Remaining individuals (not grpmax-eligible) | 0.221% | 453 |
| Middle Eastern | 0.066% | 1,515 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.0372% | 2,690 |
| African / African-American | 0.0187% | 5,356 |
| European (non-Finnish) | 0.0129% | 7,757 |
| Admixed American | 0.005% | 20,002 |
| Finnish (not grpmax-eligible) | 0.00157% | 63,722 |

*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}

**CD37** population constraint: LOEUF 1.215, pLI 2.5766e-12, missense-Z 0.52228. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 83.31, 53% of residues very-high.

## Clinical significance {#significance}

**Benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2018-03-29.

**Submitter consensus:** unanimous (2/2 Benign).

**Submission history:** 2 submissions (2018); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2018-03-29 |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |

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

## Similar variants {#similar}

Related CD37 variant pages (same residue, condition, or type): [CD37 p.Val44Met](/variant/cd37-p-val44met), [CD37 p.Ala221Thr](/variant/cd37-p-ala221thr), [CD37 p.Arg112Gly](/variant/cd37-p-arg112gly), [CD37 p.Arg112Pro](/variant/cd37-p-arg112pro), [CD37 p.Arg120Leu](/variant/cd37-p-arg120leu), [CD37 p.Arg281Cys](/variant/cd37-p-arg281cys), [CD37 p.Arg281Ser](/variant/cd37-p-arg281ser), [CD37 p.Asn170Asp](/variant/cd37-p-asn170asp).

### 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 789460). 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.*