Is CD3G p.Val131Phe (c.391G>T) pathogenic?

CD3G p.Val131Phe (c.391G>T) is classified Benign/Likely benign in CD3G (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1627); Common (popmax 50.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with combined immunodeficiency due to CD3gamma deficiency.

What condition is associated with CD3G p.Val131Phe (c.391G>T)?

CD3G p.Val131Phe (c.391G>T) is associated with combined immunodeficiency due to CD3gamma deficiency (ClinVar).

What do computational predictors say about CD3G p.Val131Phe (c.391G>T)?

AlphaMissense predicts likely benign (score 0.1627) — an in-silico prediction, not a clinical call.

CD3G p.Val131Phe

Q: How common is CD3G p.Val131Phe (c.391G>T) in the general population?

CD3G p.Val131Phe (c.391G>T) is common (popmax 50.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.391G>T · rs3753058 · VCV302685

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1627 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 50.6%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined immunodeficiency due to CD3gamma deficiency

Computational evidence

Protein change
AlphaMissense	0.1627	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -7.20	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 1.4	GERP -2.6, phastCons 0.96
Regional constraint	o/e 1.00	unconstrained · MANE · 8,042 bp · p 0.94 · regional, not allelic
Overall
CADD	16.31	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 50.6% East Asian · 22,650/44,780 alleles

Filtering AF 50% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.8%

Overall 18.1% 291,446/1,613,004 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	50.6%	2
South Asian	45.3%	2
Ashkenazi Jewishnot grpmax-eligible	23.8%	4
Middle Eastern	23.5%	4
Remaining individualsnot grpmax-eligible	20.2%	5
Finnishnot grpmax-eligible	18.3%	5
African / African-American	15.7%	6
European (non-Finnish)	15%	7
Amishnot grpmax-eligible	12.9%	8
Admixed American	10.3%	10

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.Val131Phe
Coding: c.391G>T
MANE Select: NM_000073
dbSNP: rs3753058
Type: single nucleotide variant
Location: chr11:118350635 (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 131: a UniProt-annotated variant site (in); an α-helix

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.Val131= Likely benign ★ 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 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

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-val131phe (accessed [today's date]).

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