Is CD3E p.Lys193Glu (c.577A>G) pathogenic?

CD3E p.Lys193Glu (c.577A>G) is classified Uncertain significance in CD3E (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-23). AlphaMissense: likely pathogenic (0.7084); Very rare (popmax 0.000763%, nfe); Associated with CD3E-related disorder.

What condition is associated with CD3E p.Lys193Glu (c.577A>G)?

CD3E p.Lys193Glu (c.577A>G) is associated with CD3E-related disorder (ClinVar).

How common is CD3E p.Lys193Glu (c.577A>G) in the general population?

CD3E p.Lys193Glu (c.577A>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about CD3E p.Lys193Glu (c.577A>G)?

AlphaMissense predicts likely pathogenic (score 0.7084) — an in-silico prediction, not a clinical call.

CD3E p.Lys193Glu

c.577A>G · VCV3355378

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7084 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD3E-related disorder

Computational evidence

Protein change
AlphaMissense	0.7084	likely pathogenic
REVEL	0.226	benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.052 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,760 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,410 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.Lys193Glu
Coding: c.577A>G
MANE Select: NM_000733
Type: single nucleotide variant
Location: chr11:118315495 (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 193: an α-helix; the itam domain; the 'disordered' region

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

Disease context

CD3E-related disorder

Similar variants

CD3E p.Lys193= Likely benign ★ same residue
CD3E c.103+1G>A Likely pathogenic ★★ same type
CD3E c.49+1G>C Pathogenic ★★ same type
CD3E p.Tyr96Ter Pathogenic/Likely pathogenic ★★ same type
CD3E c.520+5G>A Uncertain significance ★★ same type
CD3E p.Arg192Gln Uncertain significance ★★ ⚠ same type
CD3E p.Arg206His Uncertain significance ★★ ⚠ same type
CD3E p.Asn25Asp Uncertain significance ★★ ⚠ same type

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-lys193glu (accessed [today's date]).

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