Is CD3D p.Ala119Asp (c.356C>A) pathogenic?

CD3D p.Ala119Asp (c.356C>A) is classified Uncertain significance in CD3D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.904); Absent from gnomAD v4.1; Associated with immunodeficiency 19.

What condition is associated with CD3D p.Ala119Asp (c.356C>A)?

CD3D p.Ala119Asp (c.356C>A) is associated with immunodeficiency 19 (ClinVar).

How common is CD3D p.Ala119Asp (c.356C>A) in the general population?

CD3D p.Ala119Asp (c.356C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD3D p.Ala119Asp (c.356C>A)?

AlphaMissense predicts likely pathogenic (score 0.904) — an in-silico prediction, not a clinical call.

CD3D p.Ala119Asp

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.356C>A · rs1948284280 · VCV1519670

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.904 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

immunodeficiency 19

Computational evidence

Protein change
AlphaMissense	0.904	likely pathogenic · top 3% in CD3D
REVEL	0.383	indeterminate
SaProt	LLR -14.98	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,442 bp · p 0.64 · regional, not allelic
Overall
CADD	29.4	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: CD3D
Protein: p.Ala119Asp
Coding: c.356C>A
MANE Select: NM_000732
dbSNP: rs1948284280
Type: single nucleotide variant
Location: chr11:118339825 (GRCh38)
Gene constraint: LOEUF 1.325 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.57 · 31 PDB
Residue 119: an α-helix

Full CD3D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 19 — 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

CD3D p.Ala119Val Uncertain significance ★ ⚠ same residue
CD3D c.274+5G>A Pathogenic/Likely pathogenic ★★ same condition
CD3D c.407-2A>G Likely pathogenic ★★ same condition
CD3D p.Arg68Ter Pathogenic ★★ same condition
CD3D p.Cys93Ter Pathogenic ★★ same condition
CD3D c.274+4C>T Uncertain significance ★★ same condition
CD3D c.450+6C>T Uncertain significance ★★ same condition
CD3D p.Arg169Gln 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/cd3d-p-ala119asp (accessed [today's date]).

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