Is CD3G p.Ala137Ser (c.409G>T) pathogenic?

CD3G p.Ala137Ser (c.409G>T) is classified Uncertain significance in CD3G (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.1649); Very rare (popmax 0.000169%, nfe).

How common is CD3G p.Ala137Ser (c.409G>T) in the general population?

CD3G p.Ala137Ser (c.409G>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CD3G p.Ala137Ser (c.409G>T)?

AlphaMissense predicts likely benign (score 0.1649) — an in-silico prediction, not a clinical call.

CD3G p.Ala137Ser

c.409G>T · rs2496901907 · VCV3140585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1649	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -5.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 8,042 bp · p 0.94 · regional, not allelic
Overall
CADD	23.4	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 0.000169% European (non-Finnish) · 2/1,179,966 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,856 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: CD3G
Protein: p.Ala137Ser
Coding: c.409G>T
MANE Select: NM_000073
dbSNP: rs2496901907
Type: single nucleotide variant
Location: chr11:118350653 (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

Similar variants

CD3G c.55+1G>T Likely pathogenic ★★ same type
CD3G c.56-1G>A Likely pathogenic ★★ same type
CD3G p.Lys69Ter Pathogenic ★★ same type
CD3G p.Met1Val Pathogenic/Likely pathogenic ★★ same type
CD3G c.*308G>A Uncertain significance ★★ same type
CD3G p.Arg146Thr Uncertain significance ★★ ⚠ same type
CD3G p.Arg166Gln Uncertain significance ★★ ⚠ same type
CD3G p.Asn156Ser Uncertain significance ★★ ⚠ same type

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-ala137ser (accessed [today's date]).

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