Is CD3G p.Leu12= (c.36G>A) pathogenic?

CD3G p.Leu12= (c.36G>A) is classified Conflicting classifications of pathogenicity in CD3G (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-24). Rare (popmax 0.2%, mid); Associated with combined immunodeficiency due to CD3gamma deficiency.

What condition is associated with CD3G p.Leu12= (c.36G>A)?

CD3G p.Leu12= (c.36G>A) is associated with combined immunodeficiency due to CD3gamma deficiency (ClinVar).

How common is CD3G p.Leu12= (c.36G>A) in the general population?

CD3G p.Leu12= (c.36G>A) is rare (popmax 0.2%, mid) (gnomAD).

CD3G p.Leu12=

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.36G>A · rs181713283 · VCV649896

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.2%, mid)

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 1.2	GERP 0.88, phastCons 0.99
Overall
CADD	3.487	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.2% Middle Eastern · 12/6,004 alleles

Filtering AF 0.115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0904%

Overall 0.016% 251/1,570,588 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.2%	500
Admixed American	0.0623%	1,606
Ashkenazi Jewishnot grpmax-eligible	0.0591%	1,692
South Asian	0.0364%	2,751
Remaining individualsnot grpmax-eligible	0.0328%	3,044
African / African-American	0.0134%	7,437
European (non-Finnish)	0.0111%	9,040

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.Leu12=
Coding: c.36G>A
MANE Select: NM_000073
dbSNP: rs181713283
Type: single nucleotide variant
Location: chr11:118344459 (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-leu12 (accessed [today's date]).

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