Is CD3G p.Met1Val (c.1A>G) pathogenic?

CD3G p.Met1Val (c.1A>G) is classified Pathogenic/Likely pathogenic in CD3G (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-04). Very rare (popmax 0.000173%, nfe); Associated with combined immunodeficiency due to CD3gamma deficiency.

What condition is associated with CD3G p.Met1Val (c.1A>G)?

CD3G p.Met1Val (c.1A>G) is associated with combined immunodeficiency due to CD3gamma deficiency (ClinVar).

How common is CD3G p.Met1Val (c.1A>G) in the general population?

CD3G p.Met1Val (c.1A>G) is very rare (popmax 0.000173%, nfe) (gnomAD).

CD3G p.Met1Val

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.1A>G · rs104894199 · VCV12753

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000173%, nfe)

Conditions

combined immunodeficiency due to CD3gamma deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.365	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.7, phastCons 1
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000173% European (non-Finnish) · 2/1,156,396 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000212% 3/1,416,682 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00164%	60,864
European (non-Finnish)grpmax	0.000173%	578,198

Remaining individuals 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: CD3G
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_000073
dbSNP: rs104894199
Type: single nucleotide variant
Location: chr11:118344424 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.05 · 38 PDB

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 p.Met1Lys Likely pathogenic ★ same residue
CD3G p.Met1Thr Likely pathogenic ★ same residue
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 c.*308G>A Uncertain significance ★★ same condition
CD3G p.Arg146Thr Uncertain significance ★★ ⚠ same condition
CD3G p.Arg166Gln 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-met1val (accessed [today's date]).

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