Is CD3G p.Gln98His (c.294A>T) pathogenic?

CD3G p.Gln98His (c.294A>T) is classified Uncertain significance in CD3G (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-21). AlphaMissense: likely benign (0.3101); Ultra-rare (popmax 0.0495%, mid); Associated with combined immunodeficiency due to CD3gamma deficiency.

What condition is associated with CD3G p.Gln98His (c.294A>T)?

CD3G p.Gln98His (c.294A>T) is associated with combined immunodeficiency due to CD3gamma deficiency (ClinVar).

How common is CD3G p.Gln98His (c.294A>T) in the general population?

CD3G p.Gln98His (c.294A>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about CD3G p.Gln98His (c.294A>T)?

AlphaMissense predicts likely benign (score 0.3101) — an in-silico prediction, not a clinical call.

CD3G p.Gln98His

Q: How is Combined immunodeficiency due to CD3gamma deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.294A>T · rs201795915 · VCV1504218

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3101 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined immunodeficiency due to CD3gamma deficiency

Computational evidence

Protein change
AlphaMissense	0.3101	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -5.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.14	GERP -3.7
Regional constraint	o/e 1.00	unconstrained · MANE · 8,042 bp · p 0.94 · regional, not allelic
Overall
CADD	4.869	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 0.0495% Middle Eastern · 3/6,060 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.00428% 69/1,612,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,020
Remaining individualsnot grpmax-eligible	0.0144%	6,941
Admixed American	0.00666%	15,007
African / African-American	0.00533%	18,751
European (non-Finnish)	0.00407%	24,562
South Asian	0.0011%	91,056

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: CD3G
Protein: p.Gln98His
Coding: c.294A>T
MANE Select: NM_000073
dbSNP: rs201795915
Type: single nucleotide variant
Location: chr11:118349957 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.05 · 38 PDB
Residue 98: a β-strand

Full CD3G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to CD3gamma deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to CD3gamma deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CD3G c.55+1G>T Likely pathogenic ★★ same condition
CD3G c.56-1G>A Likely pathogenic ★★ same condition
CD3G p.Lys69Ter Pathogenic ★★ same condition
CD3G p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
CD3G c.*308G>A Uncertain significance ★★ same condition
CD3G p.Arg146Thr Uncertain significance ★★ ⚠ same condition
CD3G p.Arg166Gln Uncertain significance ★★ ⚠ same condition
CD3G p.Asn156Ser 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/cd3g-p-gln98his (accessed [today's date]).

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