Is CD3E p.Arg192Gln (c.575G>A) pathogenic?

CD3E p.Arg192Gln (c.575G>A) is classified Uncertain significance in CD3E (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-12-18). AlphaMissense: ambiguous (0.3794); Very rare (popmax 0.0044%, sas); Associated with Inborn genetic diseases.

What condition is associated with CD3E p.Arg192Gln (c.575G>A)?

CD3E p.Arg192Gln (c.575G>A) is associated with Inborn genetic diseases, immunodeficiency 18 (ClinVar).

How common is CD3E p.Arg192Gln (c.575G>A) in the general population?

CD3E p.Arg192Gln (c.575G>A) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about CD3E p.Arg192Gln (c.575G>A)?

AlphaMissense predicts ambiguous (score 0.3794) — an in-silico prediction, not a clinical call.

CD3E p.Arg192Gln

c.575G>A · rs202052957 · VCV646469

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3794 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3794	ambiguous
REVEL	0.249	benign-leaning
SaProt	LLR -5.37	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.052 · regional, not allelic
Overall
CADD	32.0	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 0.0044% South Asian · 4/90,816 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.0044% 71/1,612,954 alleles · very rare exomes 64/1,461,322 · genomes 7/151,632 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0811%	1,233
Remaining individualsnot grpmax-eligible	0.0048%	20,821
South Asiangrpmax	0.0044%	22,704
Admixed American	0.00334%	29,967
Finnishnot grpmax-eligible	0.00313%	31,940
European (non-Finnish)	0.00288%	34,698
African / African-American	0.00268%	37,342

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg192Gln
Coding: c.575G>A
MANE Select: NM_000733
dbSNP: rs202052957
Type: single nucleotide variant
Location: chr11:118315493 (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 192: the itam domain; the 'disordered' region; the 'numb-binding region' region

Full CD3E 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 18

Similar variants

CD3E p.Arg192Pro Uncertain significance ★ ⚠ same residue
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.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-arg192gln (accessed [today's date]).

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