Is CD3E p.Leu147= (c.441G>A) pathogenic?

CD3E p.Leu147= (c.441G>A) is classified Conflicting classifications of pathogenicity in CD3E (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-02). Rare (popmax 0.238%, eas); Associated with immunodeficiency 18.

What condition is associated with CD3E p.Leu147= (c.441G>A)?

CD3E p.Leu147= (c.441G>A) is associated with immunodeficiency 18 (ClinVar).

How common is CD3E p.Leu147= (c.441G>A) in the general population?

CD3E p.Leu147= (c.441G>A) is rare (popmax 0.238%, eas) (gnomAD).

CD3E p.Leu147=

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.441G>A · rs528492194 · VCV877998

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.238%, 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 -0.41	GERP -4
Overall
CADD	5.051	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.238% East Asian · 107/44,882 alleles

Filtering AF 0.202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.188%

Overall 0.00688% 111/1,614,136 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.238%	419
Remaining individualsnot grpmax-eligible	0.0064%	15,626

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.Leu147=
Coding: c.441G>A
MANE Select: NM_000733
dbSNP: rs528492194
Type: single nucleotide variant
Location: chr11:118313795 (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 147: an α-helix

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.Leu147Val Uncertain significance ★ ⚠ same residue
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

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-leu147 (accessed [today's date]).

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