Is CD3E c.*55C>A pathogenic?

CD3E c.55C>A is classified Benign in CD3E (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-08-26). Common (popmax 13.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency 18.

What condition is associated with CD3E c.*55C>A?

CD3E c.*55C>A is associated with immunodeficiency 18 (ClinVar).

CD3E c.*55C>A

Q: How common is CD3E c.*55C>A in the general population?

CD3E c.*55C>A is common (popmax 13.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.

rs2231450 · VCV302666

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 13.1%, afr) — too common for a highly-penetrant pathogenic allele

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 0.074	GERP 0.14
Overall
CADD	13.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.1% African / African-American · 9,226/70,504 alleles

Filtering AF 12.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.8%

Overall 3.1% 43,702/1,407,504 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.1%	8
Ashkenazi Jewishnot grpmax-eligible	5.15%	19
Middle Eastern	4.03%	25
Remaining individualsnot grpmax-eligible	3.58%	28
Finnishnot grpmax-eligible	3.32%	30
European (non-Finnish)	2.67%	37
Admixed American	2.62%	38
Amishnot grpmax-eligible	0.768%	130
South Asian	0.573%	175

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
Coding: c.*55C>A
MANE Select: NM_000733
dbSNP: rs2231450
Type: single nucleotide variant
Location: chr11:118315597 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.47 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.56 · 44 PDB

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-c-star-55c-a (accessed [today's date]).

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