Is CD3G p.Arg180= (c.540G>A) pathogenic?

CD3G p.Arg180= (c.540G>A) is classified Likely benign in CD3G (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-14). Very rare (popmax 0.00127%, nfe); Associated with combined immunodeficiency due to CD3gamma deficiency.

What condition is associated with CD3G p.Arg180= (c.540G>A)?

CD3G p.Arg180= (c.540G>A) is associated with combined immunodeficiency due to CD3gamma deficiency (ClinVar).

How common is CD3G p.Arg180= (c.540G>A) in the general population?

CD3G p.Arg180= (c.540G>A) is very rare (popmax 0.00127%, nfe) (gnomAD).

CD3G p.Arg180=

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.540G>A · VCV4743761

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.8	GERP 0.77, phastCons 1
Overall
CADD	6.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,179,812 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00093% 15/1,613,714 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.Arg180=
Coding: c.540G>A
MANE Select: NM_000073
Type: single nucleotide variant
Location: chr11:118352460 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.05 · 38 PDB

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.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
CD3G p.Arg166Gln Uncertain significance ★★ ⚠ same condition
CD3G p.Asn156Ser 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-arg180 (accessed [today's date]).

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