Is PLCB1 p.Ser487Phe (c.1460C>T) pathogenic?

PLCB1 p.Ser487Phe (c.1460C>T) is classified Uncertain significance in PLCB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-01-03). AlphaMissense: likely benign (0.182); Very rare (popmax 0.00119%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PLCB1 p.Ser487Phe (c.1460C>T)?

PLCB1 p.Ser487Phe (c.1460C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 12 (ClinVar).

How common is PLCB1 p.Ser487Phe (c.1460C>T) in the general population?

PLCB1 p.Ser487Phe (c.1460C>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about PLCB1 p.Ser487Phe (c.1460C>T)?

AlphaMissense predicts likely benign (score 0.182) — an in-silico prediction, not a clinical call.

PLCB1 p.Ser487Phe

c.1460C>T · rs1376374003 · VCV1419289

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.182 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.182	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -9.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 9,618 bp · p 0.07 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,962 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000867% 14/1,613,918 alleles · very rare

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.Ser487Phe
Coding: c.1460C>T
MANE Select: NM_015192
dbSNP: rs1376374003
Type: single nucleotide variant
Location: chr20:8717795 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 487: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 12

Similar variants

PLCB1 p.Ser487Tyr 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-ser487phe (accessed [today's date]).

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