Is PLCB1 p.Ser679fs (c.2036_2039del) pathogenic?

PLCB1 p.Ser679fs (c.20362039del) is classified Likely pathogenic in PLCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-30). Absent from gnomAD; Associated with developmental and epileptic encephalopathy, 12.

What condition is associated with PLCB1 p.Ser679fs (c.2036_2039del)?

PLCB1 p.Ser679fs (c.2036_2039del) is associated with developmental and epileptic encephalopathy, 12 (ClinVar).

How common is PLCB1 p.Ser679fs (c.2036_2039del) in the general population?

PLCB1 p.Ser679fs (c.2036_2039del) is absent from gnomAD (gnomAD).

PLCB1 p.Ser679fs

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.2036_2039del · rs1568577135 · VCV625996

Likely pathogenic Single submitter

Classification

Likely 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 19 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.51	GERP -3.5, phastCons 0.25

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.Ser679fs
Coding: c.2036_2039del
MANE Select: NM_015192
dbSNP: rs1568577135
Type: Deletion
Location: chr20:8733382 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 679: the c2 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 p.Ser679= Likely benign ★ same residue
PLCB1 p.Asp363fs Pathogenic ★ same condition
PLCB1 p.Gln719fs Pathogenic ★ same condition
PLCB1 p.Glu190fs Pathogenic ★ same condition
PLCB1 p.Lys1119fs Pathogenic ★ same condition
PLCB1 p.Lys889fs Pathogenic ★ same condition
PLCB1 p.Ser323fs Pathogenic ★ same condition
PLCB1 p.Ser1187fs 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-ser679fs (accessed [today's date]).

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