Is PLCB1 p.Arg561fs (c.1678dup) pathogenic?

PLCB1 p.Arg561fs (c.1678dup) is classified Pathogenic in PLCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-30). No gnomAD frequency available for this variant; Associated with developmental and epileptic encephalopathy, 12.

What condition is associated with PLCB1 p.Arg561fs (c.1678dup)?

PLCB1 p.Arg561fs (c.1678dup) is associated with developmental and epileptic encephalopathy, 12 (ClinVar).

How common is PLCB1 p.Arg561fs (c.1678dup) in the general population?

PLCB1 p.Arg561fs (c.1678dup) is no gnomAD frequency available for this variant (gnomAD).

PLCB1 p.Arg561fs

Q: How is Epilepsy of infancy with migrating focal seizures inherited?

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

c.1678dup · rs2515281114 · VCV2020515

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

developmental and epileptic encephalopathy, 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 16 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PLCB1
Protein: p.Arg561fs
Coding: c.1678dup
MANE Select: NM_015192
dbSNP: rs2515281114
Type: Duplication
Location: chr20:8724747 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 561: the pi-plc y-box domain

Full PLCB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Epilepsy of infancy with migrating focal seizures (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

PLCB1 c.1336-13dup Likely benign ★ same condition
PLCB1 c.2308+11dup Likely benign ★ same condition
PLCB1 c.862+7dup Likely benign ★ same condition
PLCB1 p.Arg222Ter Pathogenic/Likely pathogenic ★★ same condition
PLCB1 p.Arg815Ter Pathogenic/Likely pathogenic ★★ same condition
PLCB1 c.3336+3A>G Uncertain significance ★★ same condition
PLCB1 p.Ala1046Ser Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala1046Thr 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/plcb1-p-arg561fs (accessed [today's date]).

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