Is CD3E p.Ser77Asn (c.230G>A) pathogenic?

CD3E p.Ser77Asn (c.230G>A) is classified Uncertain significance in CD3E (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-05). AlphaMissense: likely benign (0.0786); Ultra-rare (popmax 0.0535%, eas); Associated with immunodeficiency 18.

What condition is associated with CD3E p.Ser77Asn (c.230G>A)?

CD3E p.Ser77Asn (c.230G>A) is associated with immunodeficiency 18 (ClinVar).

How common is CD3E p.Ser77Asn (c.230G>A) in the general population?

CD3E p.Ser77Asn (c.230G>A) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

What do computational predictors say about CD3E p.Ser77Asn (c.230G>A)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

CD3E p.Ser77Asn

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.230G>A · rs202007244 · VCV1037281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 18

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -1.6
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.052 · regional, not allelic
Overall
CADD	0.011	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0535% East Asian · 24/44,890 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00149% 24/1,614,166 alleles · ultra-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.Ser77Asn
Coding: c.230G>A
MANE Select: NM_000733
dbSNP: rs202007244
Type: single nucleotide variant
Location: chr11:118312744 (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 77: a disulfide bond; a β-strand; 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 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-p-ser77asn (accessed [today's date]).

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