# NM_000073.3(CD3G):c.213del (p.Lys71fs)

https://sugi.bio/variant/cd3g-p-lys71fs

## Summary

**CD3G p.Lys71fs (c.213del)** is classified **Pathogenic/Likely pathogenic** in CD3G (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0337%, eas); Associated with combined immunodeficiency due to CD3gamma deficiency.

**At a glance:** Pathogenic/Likely pathogenic · review: Multiple submitters · rsID rs570768621 · 3 submitters · 2 linked conditions · ultra-rare (popmax 0.0337%, eas)

## For patients & families {#patients}

This is a change in the CD3G gene that is considered likely disease-causing, submitted by 3 submitters, and is linked to combined immunodeficiency due to CD3gamma deficiency.

*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.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |
| Age of onset (of this condition) | Infancy |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0017046/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CD3G](https://sugi.bio/atlas/gene/CD3G/) |
| Protein change (HGVS p.) | p.Lys71fs |
| Coding change (HGVS c.) | c.213del |
| dbSNP | [rs570768621](https://www.ncbi.nlm.nih.gov/snp/rs570768621/) |
| Variant type | Deletion |
| Location | chr11:118349868-118349868 (GRCh38) |
| ClinVar | [VCV541654](https://www.ncbi.nlm.nih.gov/clinvar/variation/541654/) |

**All HGVS expressions:** `LRG_39:g.10533del`, `NC_000011.10:g.118349876del`, `NC_000011.9:g.118220591del`, `NG_007566.1:g.10533del`, `NM_000073.2:c.213delA`, `NM_000073.3:c.213del`

## 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 -1.699, GERP -3.63 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. For a truncating variant the loss-of-function impact is position-dependent — C-terminal / last-exon truncations may escape nonsense-mediated decay. *Descriptive; not an applied PVS1 code.*
- CADD: **PHRED 12.32**. 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 looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **0.0337%** (eas) · FAF95 0.0207% · FAF99 0.0167% · 15/44,536 in the highest group · 99/1,599,382 alleles overall — ultra-rare (popmax 0.0337%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| East Asian (grpmax) | 0.0337% | 2,969 |
| Middle Eastern | 0.0166% | 6,016 |
| European (non-Finnish) | 0.00633% | 15,789 |
| Remaining individuals (not grpmax-eligible) | 0.00484% | 20,643 |
| South Asian | 0.00331% | 30,252 |
| Admixed American | 0.00167% | 59,740 |
| Finnish (not grpmax-eligible) | 0.00158% | 63,416 |
| African / African-American | 0.00135% | 74,296 |

*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.*

## Clinical significance {#significance}

**Pathogenic/Likely pathogenic** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-01-28.

**Submitter consensus:** conflicting (2 Likely pathogenic, 1 Pathogenic).

**Submission history:** 3 submissions (2022–2026); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Pathogenic | criteria provided, single submitter | clinical testing | 2026-01-28 |
| Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Likely pathogenic | criteria provided, single submitter | clinical testing | 2022-08-08 |
| Fulgent Genetics, Fulgent Genetics | Likely pathogenic | criteria provided, single submitter | clinical testing | 2024-03-24 |

## Associated conditions {#conditions}

[combined immunodeficiency due to CD3gamma deficiency](https://sugi.bio/atlas/disease/combined-immunodeficiency-due-to-cd3gamma-deficiency/), [severe combined immunodeficiency](https://sugi.bio/atlas/disease/severe-combined-immunodeficiency/).

**Reported phenotype names (ClinVar):** Combined immunodeficiency due to CD3gamma deficiency, Severe combined immunodeficiency disease, Immunodeficiency 17, SCID-LIKE IMMUNODEFICIENCY, T CELL-PARTIAL, B CELL-POSITIVE, NK CELL-POSITIVE, Immunodeficiency 17, CD3 gamma deficient, CD3-GAMMA DEFICIENCY, Severe Combined Immune Deficiency, Severe combined immunodeficiency.

### 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 541654). 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.*