Is PLCB1 p.Glu1122= (c.3366A>G) pathogenic?

PLCB1 p.Glu1122= (c.3366A>G) is classified Likely benign in PLCB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-24). Very rare (popmax 0.00935%, afr); Associated with developmental and epileptic encephalopathy, 12.

What condition is associated with PLCB1 p.Glu1122= (c.3366A>G)?

PLCB1 p.Glu1122= (c.3366A>G) is associated with developmental and epileptic encephalopathy, 12 (ClinVar).

How common is PLCB1 p.Glu1122= (c.3366A>G) in the general population?

PLCB1 p.Glu1122= (c.3366A>G) is very rare (popmax 0.00935%, afr) (gnomAD).

PLCB1 p.Glu1122=

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.3366A>G · rs762035591 · VCV714369

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

developmental and epileptic encephalopathy, 12

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 3.4	GERP -0.7, phastCons 1
Overall
CADD	8.635	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,836 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000993% 16/1,611,876 alleles · very rare exomes 15/1,459,628 · genomes 1/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,691
Remaining individualsnot grpmax-eligible	0.00642%	15,587
Admixed American	0.005%	19,984
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590
European (non-Finnish)	8.48e-05%	1,178,596

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: PLCB1
Protein: p.Glu1122=
Coding: c.3366A>G
MANE Select: NM_015192
dbSNP: rs762035591
Type: single nucleotide variant
Location: chr20:8790204 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55

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.Glu1122Lys Uncertain significance ★ same residue
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
PLCB1 p.Ala1116Val Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala1182Val 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-glu1122 (accessed [today's date]).

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