Is CD3D p.Asn38Lys (c.114T>A) pathogenic?

CD3D p.Asn38Lys (c.114T>A) is classified Uncertain significance in CD3D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-02). AlphaMissense: ambiguous (0.4555); Ultra-rare (popmax 0.035%, amr); Associated with immunodeficiency 19.

What condition is associated with CD3D p.Asn38Lys (c.114T>A)?

CD3D p.Asn38Lys (c.114T>A) is associated with immunodeficiency 19 (ClinVar).

How common is CD3D p.Asn38Lys (c.114T>A) in the general population?

CD3D p.Asn38Lys (c.114T>A) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about CD3D p.Asn38Lys (c.114T>A)?

AlphaMissense predicts ambiguous (score 0.4555) — an in-silico prediction, not a clinical call.

CD3D p.Asn38Lys

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.114T>A · rs193284900 · VCV845145

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4555 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

immunodeficiency 19

Computational evidence

Protein change
AlphaMissense	0.4555	ambiguous
REVEL	0.17	moderately benign-leaning
SaProt	LLR -8.49	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -3.3
Regional constraint	o/e 0.97	unconstrained · MANE · 3,442 bp · p 0.64 · regional, not allelic
Overall
CADD	8.29	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 0.035% Admixed American · 21/60,006 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00136% 22/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,857
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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: CD3D
Protein: p.Asn38Lys
Coding: c.114T>A
MANE Select: NM_000732
dbSNP: rs193284900
Type: single nucleotide variant
Location: chr11:118340535 (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 38: a disulfide bond

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.Asn38Asp 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.Ala119Asp 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-asn38lys (accessed [today's date]).

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