Is CD3D p.Glu83Gly (c.248A>G) pathogenic?

CD3D p.Glu83Gly (c.248A>G) is classified Uncertain significance in CD3D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.1426); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with CD3D p.Glu83Gly (c.248A>G)?

CD3D p.Glu83Gly (c.248A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CD3D p.Glu83Gly (c.248A>G) in the general population?

CD3D p.Glu83Gly (c.248A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CD3D p.Glu83Gly (c.248A>G)?

AlphaMissense predicts likely benign (score 0.1426) — an in-silico prediction, not a clinical call.

CD3D p.Glu83Gly

c.248A>G · rs2496872089 · VCV3140582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1426 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1426	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -9.08	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 -7.2	GERP -4
Regional constraint	o/e 0.97	unconstrained · MANE · 3,442 bp · p 0.64 · regional, not allelic
Overall
CADD	0.001	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 0.00329% South Asian · 3/91,078 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000205% 3/1,461,786 alleles · very 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: CD3D
Protein: p.Glu83Gly
Coding: c.248A>G
MANE Select: NM_000732
dbSNP: rs2496872089
Type: single nucleotide variant
Location: chr11:118340401 (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

Similar variants

CD3D p.Glu83Lys Uncertain significance ★★ ⚠ same residue
CD3D p.Arg169Trp Uncertain significance ★★ ⚠ same condition
CD3D p.Arg63His Uncertain significance ★★ ⚠ same condition
CD3D p.Glu129Gly Uncertain significance ★★ ⚠ same condition
CD3D p.His128Asn Uncertain significance ★★ ⚠ same condition
CD3D p.Ile78Thr Uncertain significance ★★ ⚠ same condition
CD3D p.Lys82Glu Uncertain significance ★★ ⚠ same condition
CD3D p.Thr56Arg 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-glu83gly (accessed [today's date]).

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