Is CD3E p.Asp72= (c.216T>C) pathogenic?

CD3E p.Asp72= (c.216T>C) is classified Benign in CD3E (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Low-frequency (popmax 2.59%, eas); Associated with immunodeficiency 18.

What condition is associated with CD3E p.Asp72= (c.216T>C)?

CD3E p.Asp72= (c.216T>C) is associated with immunodeficiency 18 (ClinVar).

How common is CD3E p.Asp72= (c.216T>C) in the general population?

CD3E p.Asp72= (c.216T>C) is low-frequency (popmax 2.59%, eas) (gnomAD).

CD3E p.Asp72=

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.216T>C · rs2231444 · VCV136690

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.59%, eas)

Conditions

immunodeficiency 18

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 -1.4	GERP -2.6
Overall
CADD	1.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.59% East Asian · 1,162/44,890 alleles

Filtering AF 2.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.42%

Overall 0.0884% 1,427/1,614,064 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.59%	39
Remaining individualsnot grpmax-eligible	0.262%	381
African / African-American	0.072%	1,388
Admixed American	0.0183%	5,456
South Asian	0.00549%	18,215
European (non-Finnish)	0.00263%	38,065

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: CD3E
Protein: p.Asp72=
Coding: c.216T>C
MANE Select: NM_000733
dbSNP: rs2231444
Type: single nucleotide variant
Location: chr11:118312730 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.47 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.56 · 44 PDB
Residue 72: a disulfide bond; the ig-like domain

Full CD3E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 18 — 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

CD3E c.103+1G>A Likely pathogenic ★★ same condition
CD3E c.49+1G>C Pathogenic ★★ same condition
CD3E p.Tyr96Ter Pathogenic/Likely pathogenic ★★ same condition
CD3E c.520+5G>A Uncertain significance ★★ same condition
CD3E p.Arg192Gln Uncertain significance ★★ ⚠ same condition
CD3E p.Arg206His Uncertain significance ★★ ⚠ same condition
CD3E p.Asn25Asp Uncertain significance ★★ ⚠ same condition
CD3E p.Asn74Thr 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/cd3e-p-asp72 (accessed [today's date]).

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