# NM_001783.4(CD79A):c.372C>T (p.Arg124=)

https://sugi.bio/variant/cd79a-p-arg124

## Summary

**CD79A p.Arg124= (c.372C>T)** is classified **Likely benign** in CD79A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-03). Very rare (popmax 0.00924%, nfe); Associated with agammaglobulinemia 3, autosomal recessive.

**At a glance:** Likely benign · review: Multiple submitters · rsID rs377615732 · 3 submitters · 1 linked condition · very rare (popmax 0.00924%, nfe)

## For patients & families {#patients}

This is a change in the CD79A gene that is classified as likely benign — not considered disease-causing, submitted by 3 submitters, and is linked to agammaglobulinemia 3, autosomal recessive.

*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:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0015673/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CD79A](https://sugi.bio/atlas/gene/CD79A/) |
| Protein change (HGVS p.) | p.Arg124= |
| Coding change (HGVS c.) | c.372C>T |
| MANE Select transcript | [NM_001783](https://www.ncbi.nlm.nih.gov/nuccore/NM_001783) |
| dbSNP | [rs377615732](https://www.ncbi.nlm.nih.gov/snp/rs377615732/) |
| Variant type | single nucleotide variant |
| Location | chr19:41879282-41879282 (GRCh38) |
| ClinVar | [VCV1640099](https://www.ncbi.nlm.nih.gov/clinvar/variation/1640099/) |

**All HGVS expressions:** `LRG_42:g.7163C>T`, `NC_000019.10:g.41879282C>T`, `NC_000019.9:g.42383352C>T`, `NG_009619.1:g.7163C>T`, `NM_001783.4:c.372C>T`, `NM_021601.4:c.265+107C>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 -13.616, GERP -3.68 — fast-evolving / accelerated position
- CADD: **PHRED 0.674**. 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>G, Δ0.82 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 **0.00924%** (nfe) · FAF95 0.00782% · FAF99 0.00728% · 109/1,179,904 in the highest group · 118/1,612,182 alleles overall — very rare (popmax 0.00924%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| European (non-Finnish) (grpmax) | 0.00924% | 10,825 |
| Remaining individuals (not grpmax-eligible) | 0.00801% | 12,489 |
| East Asian | 0.00668% | 14,963 |
| South Asian | 0.0011% | 91,074 |

*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}

**CD79A** population constraint: LOEUF 0.991, pLI 0.0010109, missense-Z 1.1783. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **agammaglobulinemia 3, autosomal recessive** — Definitive (AR)

## Protein context {#protein}

Residue **124** lies in a β-strand.

AlphaFold model confidence (whole protein): pLDDT 77.56, 39% of residues very-high.

**6 experimental structure(s)** (PDB): [1CV9](https://www.rcsb.org/structure/1CV9), [7WSO](https://www.rcsb.org/structure/7WSO), [7WSP](https://www.rcsb.org/structure/7WSP), [7XQ8](https://www.rcsb.org/structure/7XQ8), [7XT6](https://www.rcsb.org/structure/7XT6), [9E6G](https://www.rcsb.org/structure/9E6G).

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

*Describes the biological roles of CD79A (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:** CD79A's established molecular role includes identical protein binding. In Reactome, CD79A is annotated in disease pathway(s) including **Potential therapeutics for SARS**.

**Disease mechanism (Reactome):** CD79A loss or alteration is curated in [Potential therapeutics for SARS](https://reactome.org/content/detail/R-HSA-9679191).

### Pathways affected {#pathways}

CD79A participates in **4 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Potential therapeutics for SARS](https://reactome.org/content/detail/R-HSA-9679191) | curated |
| [CD22 mediated BCR regulation](https://reactome.org/content/detail/R-HSA-5690714) | curated |
| [Affinity selection of immunoglobulins](https://reactome.org/content/detail/R-HSA-9938027) | electronic |
| [Antigen activates B Cell Receptor (BCR) leading to generation of second messengers](https://reactome.org/content/detail/R-HSA-983695) | electronic |

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

**Molecular function:** identical protein binding.

## Clinical significance {#significance}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2025-12-03.

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

**Submission history:** 3 submissions (2023–2025); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Likely Benign | criteria provided, single submitter | clinical testing | 2024-09-16 |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2025-12-03 |
| Blueprint Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2023-11-15 |

## Associated conditions {#conditions}

[agammaglobulinemia 3, autosomal recessive](https://sugi.bio/atlas/disease/agammaglobulinemia-3-autosomal-recessive/).

**Reported phenotype names (ClinVar):** Agammaglobulinemia 3, autosomal recessive, not specified, AGAMMAGLOBULINEMIA, AUTOSOMAL RECESSIVE, DUE TO CD79A DEFECT, AGAMMAGLOBULINEMIA 3, AllHighlyPenetrant.

## Similar variants {#similar}

Related CD79A variant pages (same residue, condition, or type): [CD79A p.Arg124Cys](/variant/cd79a-p-arg124cys), [CD79A p.Arg124His](/variant/cd79a-p-arg124his), [CD79A p.Arg168Gln](/variant/cd79a-p-arg168gln), [CD79A p.Arg204Gln](/variant/cd79a-p-arg204gln), [CD79A p.Asn60Ser](/variant/cd79a-p-asn60ser), [CD79A p.Asn63Ser](/variant/cd79a-p-asn63ser), [CD79A p.Gly179Arg](/variant/cd79a-p-gly179arg), [CD79A p.Ile151Thr](/variant/cd79a-p-ile151thr).

### 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 1640099). 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.*