Is CD3D p.Thr115= (c.345T>C) pathogenic?

CD3D p.Thr115= (c.345T>C) is classified Likely benign in CD3D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). Ultra-rare (popmax 0.0187%, sas); Associated with immunodeficiency 19.

What condition is associated with CD3D p.Thr115= (c.345T>C)?

CD3D p.Thr115= (c.345T>C) is associated with immunodeficiency 19 (ClinVar).

How common is CD3D p.Thr115= (c.345T>C) in the general population?

CD3D p.Thr115= (c.345T>C) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

CD3D p.Thr115=

Q: How is T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta inherited?

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

c.345T>C · VCV3674913

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Conditions

immunodeficiency 19

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 0.1	GERP -4
Overall
CADD	8.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/91,076 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.00112% 18/1,614,006 alleles · ultra-rare exomes 18/1,461,876 · genomes 0/152,130 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,357
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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: CD3D
Protein: p.Thr115=
Coding: c.345T>C
MANE Select: NM_000732
Type: single nucleotide variant
Location: chr11:118339836 (GRCh38)
Gene constraint: LOEUF 1.325 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.57 · 31 PDB
Residue 115: an α-helix

Full CD3D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 19 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CD3D p.Thr115Ser Uncertain significance ★★ same residue
CD3D p.Thr115Asn Uncertain significance ★ ⚠ same residue
CD3D p.Thr115Pro Uncertain significance ★ same residue
CD3D c.274+5G>A Pathogenic/Likely pathogenic ★★ same condition
CD3D c.407-2A>G Likely pathogenic ★★ same condition
CD3D p.Arg68Ter Pathogenic ★★ same condition
CD3D p.Cys93Ter Pathogenic ★★ same condition
CD3D c.274+4C>T 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/cd3d-p-thr115 (accessed [today's date]).

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