Is CD3G p.Ser172Ile (c.515G>T) pathogenic?

CD3G p.Ser172Ile (c.515G>T) is classified Uncertain significance in CD3G (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-22). AlphaMissense: likely pathogenic (0.7428); Ultra-rare (popmax 0.0107%, afr).

How common is CD3G p.Ser172Ile (c.515G>T) in the general population?

CD3G p.Ser172Ile (c.515G>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about CD3G p.Ser172Ile (c.515G>T)?

AlphaMissense predicts likely pathogenic (score 0.7428) — an in-silico prediction, not a clinical call.

CD3G p.Ser172Ile

c.515G>T · rs993187722 · VCV2620636

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7428 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7428	likely pathogenic
REVEL	0.379	indeterminate
SaProt	LLR -8.14	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 8,042 bp · p 0.94 · regional, not allelic
Overall
CADD	24.9	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 0.0107% African / African-American · 8/74,906 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00062% 10/1,613,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,363
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Ser172Ile
Coding: c.515G>T
MANE Select: NM_000073
dbSNP: rs993187722
Type: single nucleotide variant
Location: chr11:118352435 (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 172: an α-helix; the itam domain

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-ser172ile (accessed [today's date]).

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