Is CD3E p.Cys49Ser (c.145T>A) pathogenic?

CD3E p.Cys49Ser (c.145T>A) is classified Uncertain significance in CD3E (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely pathogenic (0.9818); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CD3E p.Cys49Ser (c.145T>A)?

CD3E p.Cys49Ser (c.145T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CD3E p.Cys49Ser (c.145T>A) in the general population?

CD3E p.Cys49Ser (c.145T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD3E p.Cys49Ser (c.145T>A)?

AlphaMissense predicts likely pathogenic (score 0.9818) — an in-silico prediction, not a clinical call.

CD3E p.Cys49Ser

c.145T>A · rs1948142016 · VCV2233779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9818 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9818	likely pathogenic · top 1% in CD3E
REVEL	0.666	pathogenic-leaning
SaProt	LLR -12.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.052 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD3E
Protein: p.Cys49Ser
Coding: c.145T>A
MANE Select: NM_000733
dbSNP: rs1948142016
Type: single nucleotide variant
Location: chr11:118312659 (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 49: a disulfide bond; the ig-like domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD3E p.Cys49= Likely benign ★ same residue
CD3E p.Arg192Gln Uncertain significance ★★ ⚠ same condition
CD3E p.Cys98Arg Uncertain significance ★★ ⚠ same condition
CD3E p.Ile133Thr Uncertain significance ★★ ⚠ same condition
CD3E p.Tyr150His Uncertain significance ★★ ⚠ same condition
CD3E p.Asn62Ile Uncertain significance ★ ⚠ same condition
CD3E p.Glu79Lys Uncertain significance ★ ⚠ same condition
CD3E p.Gly30Ser Conflicting classifications of pathogenicity ★ ⚠ 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-cys49ser (accessed [today's date]).

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