Is CD3D p.Arg169Trp (c.505C>T) pathogenic?

CD3D p.Arg169Trp (c.505C>T) is classified Uncertain significance in CD3D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-08). AlphaMissense: likely benign (0.1374); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with CD3D p.Arg169Trp (c.505C>T)?

CD3D p.Arg169Trp (c.505C>T) is associated with Inborn genetic diseases, immunodeficiency 19 (ClinVar).

How common is CD3D p.Arg169Trp (c.505C>T) in the general population?

CD3D p.Arg169Trp (c.505C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about CD3D p.Arg169Trp (c.505C>T)?

AlphaMissense predicts likely benign (score 0.1374) — an in-silico prediction, not a clinical call.

CD3D p.Arg169Trp

c.505C>T · rs367800432 · VCV962292

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1374 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1374	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -9.88	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	GERP -2.8, phastCons 0.51
Regional constraint	o/e 0.97	unconstrained · MANE · 3,442 bp · p 0.64 · regional, not allelic
Overall
CADD	23.5	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 0.0107% African / African-American · 8/74,868 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.0018% 29/1,613,816 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,358
Admixed American	0.00333%	29,995
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.00153%	65,549

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.Arg169Trp
Coding: c.505C>T
MANE Select: NM_000732
dbSNP: rs367800432
Type: single nucleotide variant
Location: chr11:118339173 (GRCh38)
Gene constraint: LOEUF 1.325 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.57 · 31 PDB

Full CD3D 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

Also linked: immunodeficiency 19

Similar variants

CD3D p.Arg169Gln 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-arg169trp (accessed [today's date]).

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