Is CD3D p.Arg68Ter (c.202C>T) pathogenic?

CD3D p.Arg68Ter (c.202C>T) is classified Pathogenic in CD3D (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-04). Very rare (popmax 0.00686%, nfe); Associated with CD3D-related disorder.

What condition is associated with CD3D p.Arg68Ter (c.202C>T)?

CD3D p.Arg68Ter (c.202C>T) is associated with CD3D-related disorder, immunodeficiency 19 (ClinVar).

How common is CD3D p.Arg68Ter (c.202C>T) in the general population?

CD3D p.Arg68Ter (c.202C>T) is very rare (popmax 0.00686%, nfe) (gnomAD).

CD3D p.Arg68Ter

c.202C>T · rs111033580 · VCV12747

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00686%, nfe)

Conditions

CD3D-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 5
REVEL	0.388	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -1.1, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00686% European (non-Finnish) · 81/1,179,990 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00533% 86/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00686%	14,568
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0032%	31,255
African / African-American	0.00267%	37,473

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.Arg68Ter
Coding: c.202C>T
MANE Select: NM_000732
dbSNP: rs111033580
Type: single nucleotide variant
Location: chr11:118340447 (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 68: a disulfide bond; a β-strand

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

Disease context

CD3D-related disorder

Also linked: immunodeficiency 19

Similar variants

CD3D p.Arg68Gly Uncertain significance ★ ⚠ same residue
CD3D p.Arg68= Likely benign ★ same residue
CD3D p.Arg68Gln 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.Cys93Ter Pathogenic ★★ same condition
CD3D c.274+4C>T Uncertain significance ★★ same condition
CD3D c.450+6C>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-arg68ter (accessed [today's date]).

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