Is CD3G p.Lys71fs (c.213del) pathogenic?

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.

How common is CD3G p.Lys71fs (c.213del) in the general population?

CD3G p.Lys71fs (c.213del) is ultra-rare (popmax 0.0337%, eas) (gnomAD).

CD3G p.Lys71fs

Q: What condition is associated with CD3G p.Lys71fs (c.213del)?

CD3G p.Lys71fs (c.213del) is associated with combined immunodeficiency due to CD3gamma deficiency, severe combined immunodeficiency (ClinVar).

Q: How is Combined immunodeficiency due to CD3gamma deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.213del · rs570768621 · VCV541654

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0337%, eas)

Conditions

combined immunodeficiency due to CD3gamma deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.7	GERP -3.6
Overall
CADD	12.32	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0337% East Asian · 15/44,536 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00619% 99/1,599,382 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0337%	2,969
Middle Eastern	0.0166%	6,016
European (non-Finnish)	0.00633%	15,789
Remaining individualsnot grpmax-eligible	0.00484%	20,643
South Asian	0.00331%	30,252
Admixed American	0.00167%	59,740
Finnishnot grpmax-eligible	0.00158%	63,416
African / African-American	0.00135%	74,296

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CD3G
Protein: p.Lys71fs
Coding: c.213del
dbSNP: rs570768621
Type: Deletion
Location: chr11:118349868 (GRCh38)

Full CD3G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to CD3gamma deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe combined immunodeficiency

For Combined immunodeficiency due to CD3gamma deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cd3g-p-lys71fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown