Is CD3D p.Val148= (c.444C>G) pathogenic?

CD3D p.Val148= (c.444C>G) is classified Likely benign in CD3D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). Very rare (popmax 0.0011%, sas); Associated with immunodeficiency 19.

What condition is associated with CD3D p.Val148= (c.444C>G)?

CD3D p.Val148= (c.444C>G) is associated with immunodeficiency 19 (ClinVar).

How common is CD3D p.Val148= (c.444C>G) in the general population?

CD3D p.Val148= (c.444C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

CD3D p.Val148=

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.444C>G · rs763565471 · VCV2912701

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

immunodeficiency 19

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.037	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.58 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.33	GERP -1.6, phastCons 0.97
Overall
CADD	5.767	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Overall 6.84e-05% 1/1,461,862 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: CD3D
Protein: p.Val148=
Coding: c.444C>G
MANE Select: NM_000732
dbSNP: rs763565471
Type: single nucleotide variant
Location: chr11:118339457 (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 148: the itam domain

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 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
CD3D c.450+6C>T Uncertain significance ★★ same condition
CD3D p.Ala119Asp Uncertain significance ★★ ⚠ same condition
CD3D p.Arg169Gln 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-val148 (accessed [today's date]).

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