Is CD3G p.Asn156= (c.468T>C) pathogenic?

CD3G p.Asn156= (c.468T>C) is classified Likely benign in CD3G (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Very rare (popmax 0.0011%, sas); Associated with combined immunodeficiency due to CD3gamma deficiency.

What condition is associated with CD3G p.Asn156= (c.468T>C)?

CD3G p.Asn156= (c.468T>C) is associated with combined immunodeficiency due to CD3gamma deficiency (ClinVar).

How common is CD3G p.Asn156= (c.468T>C) in the general population?

CD3G p.Asn156= (c.468T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

CD3G p.Asn156=

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.468T>C · VCV4725672

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

combined immunodeficiency due to CD3gamma deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -0.48, phastCons 0.99
Overall
CADD	8.037	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Overall 6.84e-05% 1/1,461,778 alleles · very rare

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.Asn156=
Coding: c.468T>C
MANE Select: NM_000073
Type: single nucleotide variant
Location: chr11:118351656 (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 156: the itam domain

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 p.Asn156Ser Uncertain significance ★★ ⚠ same residue
CD3G p.Asn156His Uncertain significance ★ ⚠ same residue
CD3G c.55+1G>T Likely pathogenic ★★ same condition
CD3G c.56-1G>A Likely pathogenic ★★ same condition
CD3G p.Lys69Ter Pathogenic ★★ same condition
CD3G p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
CD3G c.*308G>A Uncertain significance ★★ same condition
CD3G p.Arg146Thr Uncertain significance ★★ ⚠ 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-asn156 (accessed [today's date]).

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