Is CD3G p.Ile123fs (c.368del) pathogenic?

CD3G p.Ile123fs (c.368del) is classified Uncertain significance in CD3G (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). Absent from gnomAD; Associated with combined immunodeficiency due to CD3gamma deficiency.

What condition is associated with CD3G p.Ile123fs (c.368del)?

CD3G p.Ile123fs (c.368del) is associated with combined immunodeficiency due to CD3gamma deficiency (ClinVar).

How common is CD3G p.Ile123fs (c.368del) in the general population?

CD3G p.Ile123fs (c.368del) is absent from gnomAD (gnomAD).

CD3G p.Ile123fs

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.368del · rs2134070701 · VCV1354605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 4 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP -0.36, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CD3G
Protein: p.Ile123fs
Coding: c.368del
MANE Select: NM_000073
dbSNP: rs2134070701
Type: Deletion
Location: chr11:118350612 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.05 · 38 PDB
Residue 123: an α-helix

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

For Combined immunodeficiency due to CD3gamma deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CD3G c.70_79+5del Likely pathogenic ★★ same condition
CD3G c.56-2del Likely pathogenic ★ same condition
CD3G c.70_80del Likely pathogenic ★ same condition
CD3G c.308-13_308-6del Likely benign ★ same condition
CD3G c.440-19_440-18del Likely benign ★ same condition
CD3G c.440-7del Benign ★ same condition
CD3G c.483+14_483+18del Likely benign ★ same condition
CD3G c.55+1G>T Likely pathogenic ★★ same condition

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-ile123fs (accessed [today's date]).

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