Is PLCG2 p.Asp384= (c.1152C>T) pathogenic?

PLCG2 p.Asp384= (c.1152C>T) is classified Benign/Likely benign in PLCG2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-23). Rare (popmax 0.753%, afr); Associated with familial cold autoinflammatory syndrome 3.

What condition is associated with PLCG2 p.Asp384= (c.1152C>T)?

PLCG2 p.Asp384= (c.1152C>T) is associated with familial cold autoinflammatory syndrome 3 (ClinVar).

How common is PLCG2 p.Asp384= (c.1152C>T) in the general population?

PLCG2 p.Asp384= (c.1152C>T) is rare (popmax 0.753%, afr) (gnomAD).

PLCG2 p.Asp384=

Q: How is PLCG2-associated antibody deficiency and immune dysregulation inherited?

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

c.1152C>T · rs13333713 · VCV540113

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.753%, afr)

Conditions

familial cold autoinflammatory syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -4.1
Overall
CADD	0.167	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.753% African / African-American · 565/75,038 alleles

Filtering AF 0.702% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.681%

Overall 0.039% 630/1,614,110 alleles · rare exomes 321/1,461,862 · genomes 309/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.753%	133
Remaining individualsnot grpmax-eligible	0.0448%	2,233
Admixed American	0.0383%	2,609
East Asian	0.00446%	22,436
South Asian	0.0011%	91,070
European (non-Finnish)	0.000932%	107,274

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: PLCG2
Protein: p.Asp384=
Coding: c.1152C>T
MANE Select: NM_002661
dbSNP: rs13333713
Type: single nucleotide variant
Location: chr16:81895886 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.49 · 8 PDB
Residue 384: the pi-plc x-box domain; an α-helix

Full PLCG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial cold autoinflammatory syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PLCG2-associated antibody deficiency and immune dysregulation (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

PLCG2 p.Asp384Glu Uncertain significance ★ same residue
PLCG2 p.Ala708Pro Pathogenic ★★ ⚠ same condition
PLCG2 c.1467+3G>A Uncertain significance ★★ same condition
PLCG2 c.1934+1G>A Uncertain significance ★★ same condition
PLCG2 c.2235+3A>G Uncertain significance ★★ same condition
PLCG2 c.2235+5G>A Uncertain significance ★★ same condition
PLCG2 c.2307+4C>T Uncertain significance ★★ same condition
PLCG2 c.2581+5G>A 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/plcg2-p-asp384 (accessed [today's date]).

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