# NM_000626.4(CD79B):c.591G>A (p.Glu197=)

https://sugi.bio/variant/cd79b-p-glu197

## Summary

**CD79B p.Glu197= (c.591G>A)** is classified **Uncertain significance** in CD79B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). Ultra-rare (popmax 0.0201%, eas); Associated with agammaglobulinemia 6, autosomal recessive.

**At a glance:** Uncertain significance · review: Single submitter · rsID rs199859520 · 1 submitter · 1 linked condition · ultra-rare (popmax 0.0201%, eas)

## For patients & families {#patients}

This is a change in the CD79B gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter, and is linked to agammaglobulinemia 6, 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/0015579/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CD79B](https://sugi.bio/atlas/gene/CD79B/) |
| Protein change (HGVS p.) | p.Glu197= |
| Coding change (HGVS c.) | c.591G>A |
| MANE Select transcript | [NM_000626](https://www.ncbi.nlm.nih.gov/nuccore/NM_000626) |
| dbSNP | [rs199859520](https://www.ncbi.nlm.nih.gov/snp/rs199859520/) |
| Variant type | single nucleotide variant |
| Location | chr17:63929434-63929434 (GRCh38) |
| ClinVar | [VCV1418607](https://www.ncbi.nlm.nih.gov/clinvar/variation/1418607/) |

**All HGVS expressions:** `LRG_43:g.7911G>A`, `NC_000017.10:g.62006794C>T`, `NC_000017.11:g.63929434C>T`, `NG_007368.1:g.7911G>A`, `NG_042788.1:g.12342C>T`, `NM_000626.4:c.591G>A`, `NM_001039933.3:c.594G>A`, `NM_001329050.2:c.282G>A`, `NM_021602.4:c.279G>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 7.599, GERP 1.6, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 20.9**. 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, Δ0.22 donor loss), 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 **0.0201%** (eas) · FAF95 0.0104% · FAF99 0.00779% · 9/44,872 in the highest group · 12/1,613,988 alleles overall — ultra-rare (popmax 0.0201%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| East Asian (grpmax) | 0.0201% | 4,986 |
| Remaining individuals (not grpmax-eligible) | 0.0048% | 20,836 |

*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}

**CD79B** population constraint: LOEUF 0.421, pLI 0.99818, missense-Z 1.9247. *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 6, autosomal recessive** — Definitive (AR)

## Protein context {#protein}

Residue **197** lies in the itam domain.

AlphaFold model confidence (whole protein): pLDDT 76.02, 36% of residues very-high.

**6 experimental structure(s)** (PDB): [3KG5](https://www.rcsb.org/structure/3KG5), [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 CD79B (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:** CD79B's established molecular role includes identical protein binding. p.Glu197= falls in the itam domain. In Reactome, CD79B is annotated in disease pathway(s) including **Potential therapeutics for SARS**.

**Disease mechanism (Reactome):** CD79B loss or alteration is curated in [Potential therapeutics for SARS](https://reactome.org/content/detail/R-HSA-9679191).

### Pathways affected {#pathways}

CD79B 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}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2021-08-23.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Uncertain significance | criteria provided, single submitter | clinical testing | 2021-08-23 |

## Associated conditions {#conditions}

[agammaglobulinemia 6, autosomal recessive](https://sugi.bio/atlas/disease/agammaglobulinemia-6-autosomal-recessive/).

**Reported phenotype names (ClinVar):** Agammaglobulinemia 6, autosomal recessive, AGAMMAGLOBULINEMIA 6, AGAMMAGLOBULINEMIA, AUTOSOMAL RECESSIVE, DUE TO CD79B DEFECT.

## Similar variants {#similar}

Related CD79B variant pages (same residue, condition, or type): [CD79B p.Glu197Gln](/variant/cd79b-p-glu197gln), [CD79B p.Ala5Val](/variant/cd79b-p-ala5val), [CD79B p.Arg36Trp](/variant/cd79b-p-arg36trp), [CD79B p.Gly216Arg](/variant/cd79b-p-gly216arg), [CD79B p.Leu91Pro](/variant/cd79b-p-leu91pro), [CD79B p.Met96Val](/variant/cd79b-p-met96val), [CD79B p.Thr212Met](/variant/cd79b-p-thr212met), [CD79B p.Val175Met](/variant/cd79b-p-val175met).

### 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 1418607). 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.*