Is PLCB1 p.Val571= (c.1713G>C) pathogenic?

PLCB1 p.Val571= (c.1713G>C) is classified Likely benign in PLCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-09). Very rare (popmax 0.00168%, amr); Associated with developmental and epileptic encephalopathy, 12.

What condition is associated with PLCB1 p.Val571= (c.1713G>C)?

PLCB1 p.Val571= (c.1713G>C) is associated with developmental and epileptic encephalopathy, 12 (ClinVar).

How common is PLCB1 p.Val571= (c.1713G>C) in the general population?

PLCB1 p.Val571= (c.1713G>C) is very rare (popmax 0.00168%, amr) (gnomAD).

PLCB1 p.Val571=

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.1713G>C · VCV4773929

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.7	GERP 2.5, phastCons 1
Overall
CADD	10.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,404 alleles

Overall 0.000125% 2/1,605,866 alleles · very rare exomes 2/1,453,794 · genomes 0/152,072 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,404
European (non-Finnish)	8.52e-05%	1,174,016

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.Val571=
Coding: c.1713G>C
MANE Select: NM_015192
Type: single nucleotide variant
Location: chr20:8727343 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 571: 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 p.Val571Met 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-val571 (accessed [today's date]).

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