Is CD3D p.Thr115Pro (c.343A>C) pathogenic?

CD3D p.Thr115Pro (c.343A>C) is classified Uncertain significance in CD3D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-29). AlphaMissense: ambiguous (0.4264); Absent from gnomAD v4.1; Associated with immunodeficiency 19.

What condition is associated with CD3D p.Thr115Pro (c.343A>C)?

CD3D p.Thr115Pro (c.343A>C) is associated with immunodeficiency 19 (ClinVar).

How common is CD3D p.Thr115Pro (c.343A>C) in the general population?

CD3D p.Thr115Pro (c.343A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD3D p.Thr115Pro (c.343A>C)?

AlphaMissense predicts ambiguous (score 0.4264) — an in-silico prediction, not a clinical call.

CD3D p.Thr115Pro

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.343A>C · rs762023030 · VCV2133775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4264 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

immunodeficiency 19

Computational evidence

Protein change
AlphaMissense	0.4264	ambiguous
REVEL	0.419	indeterminate
SaProt	LLR -12.87	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,442 bp · p 0.64 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD3D
Protein: p.Thr115Pro
Coding: c.343A>C
MANE Select: NM_000732
dbSNP: rs762023030
Type: single nucleotide variant
Location: chr11:118339838 (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.Thr115= Likely benign ★ 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-thr115pro (accessed [today's date]).

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