Is CD3E p.Ser88fs (c.261_262del) pathogenic?

CD3E p.Ser88fs (c.261262del) is classified Pathogenic in CD3E (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-02). Very rare (popmax 0.000169%, nfe); Associated with immunodeficiency 18.

What condition is associated with CD3E p.Ser88fs (c.261_262del)?

CD3E p.Ser88fs (c.261_262del) is associated with immunodeficiency 18 (ClinVar).

How common is CD3E p.Ser88fs (c.261_262del) in the general population?

CD3E p.Ser88fs (c.261_262del) is very rare (popmax 0.000169%, nfe) (gnomAD).

CD3E p.Ser88fs

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.261_262del · rs1249197356 · VCV847887

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

immunodeficiency 18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.8	GERP -4
Overall
CADD	24.2	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 0.000169% European (non-Finnish) · 2/1,180,042 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,086 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: CD3E
Protein: p.Ser88fs
Coding: c.261_262del
MANE Select: NM_000733
dbSNP: rs1249197356
Type: Deletion
Location: chr11:118312773 (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 88: 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 p.Gly143fs Pathogenic ★ same condition
CD3E p.Gly68_Gly76del Uncertain significance ★ same condition
CD3E p.Lys177fs Uncertain significance ★ same condition
CD3E c.353-5del Benign ★ same condition
CD3E c.50-10del Likely benign ★ same condition
CD3E c.521-15del Benign ★ same condition
CD3E c.568-11_568-10del Likely benign ★ same condition
CD3E c.103+1G>A Likely pathogenic ★★ 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-ser88fs (accessed [today's date]).

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