Is PLCB1 p.Phe497= (c.1491C>T) pathogenic?

PLCB1 p.Phe497= (c.1491C>T) is classified Conflicting classifications of pathogenicity in PLCB1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-11). Rare (popmax 0.362%, afr); Associated with Inborn genetic diseases.

What condition is associated with PLCB1 p.Phe497= (c.1491C>T)?

PLCB1 p.Phe497= (c.1491C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 12 (ClinVar).

How common is PLCB1 p.Phe497= (c.1491C>T) in the general population?

PLCB1 p.Phe497= (c.1491C>T) is rare (popmax 0.362%, afr) (gnomAD).

PLCB1 p.Phe497=

c.1491C>T · rs145869401 · VCV260594

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.362%, afr)

Conditions

Inborn genetic diseases

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 -7.2	GERP -5
Overall
CADD	1.345	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.362% African / African-American · 270/74,576 alleles

Filtering AF 0.327% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.313%

Overall 0.0201% 324/1,608,882 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.362%	276
Admixed American	0.0273%	3,662
Remaining individualsnot grpmax-eligible	0.0209%	4,788
South Asian	0.0145%	6,910
East Asian	0.00223%	44,842
European (non-Finnish)	0.000933%	107,156

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.Phe497=
Coding: c.1491C>T
MANE Select: NM_015192
dbSNP: rs145869401
Type: single nucleotide variant
Location: chr20:8717826 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 497: 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.Phe497Val 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-phe497 (accessed [today's date]).

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