Is PLCG2 p.Ser16= (c.48C>T) pathogenic?

PLCG2 p.Ser16= (c.48C>T) is classified Likely benign in PLCG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-18). Absent from gnomAD v4.1; Associated with familial cold autoinflammatory syndrome 3.

What condition is associated with PLCG2 p.Ser16= (c.48C>T)?

PLCG2 p.Ser16= (c.48C>T) is associated with familial cold autoinflammatory syndrome 3 (ClinVar).

How common is PLCG2 p.Ser16= (c.48C>T) in the general population?

PLCG2 p.Ser16= (c.48C>T) is absent from gnomAD v4.1 (gnomAD).

PLCG2 p.Ser16=

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.48C>T · rs752018966 · VCV2802486

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.44	GERP -3.6, phastCons 0.15
Overall
CADD	6.463	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLCG2
Protein: p.Ser16=
Coding: c.48C>T
MANE Select: NM_002661
dbSNP: rs752018966
Type: single nucleotide variant
Location: chr16:81786037 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.49 · 8 PDB

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.Ser16Arg Uncertain significance ★★ ⚠ same residue
PLCG2 p.Ser16Gly 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

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-ser16 (accessed [today's date]).

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