Is PLCB1 p.Ser969= (c.2907C>T) pathogenic?

PLCB1 p.Ser969= (c.2907C>T) is classified Likely benign in PLCB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0884%, afr); Associated with Inborn genetic diseases.

What condition is associated with PLCB1 p.Ser969= (c.2907C>T)?

PLCB1 p.Ser969= (c.2907C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 12 (ClinVar).

How common is PLCB1 p.Ser969= (c.2907C>T) in the general population?

PLCB1 p.Ser969= (c.2907C>T) is ultra-rare (popmax 0.0884%, afr) (gnomAD).

PLCB1 p.Ser969=

c.2907C>T · rs368328261 · VCV589952

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0884%, 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 -4.4	GERP -3.5
Overall
CADD	0.328	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0884% African / African-American · 66/74,672 alleles

Filtering AF 0.0712% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.065%

Overall 0.00845% 136/1,609,622 alleles · ultra-rare exomes 95/1,457,432 · genomes 41/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0884%	1,131
Remaining individualsnot grpmax-eligible	0.0481%	2,078
Admixed American	0.0186%	5,372
South Asian	0.00895%	11,178
East Asian	0.00446%	22,425
European (non-Finnish)	0.00161%	62,045

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.Ser969=
Coding: c.2907C>T
MANE Select: NM_015192
dbSNP: rs368328261
Type: single nucleotide variant
Location: chr20:8765335 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 969: 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.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
PLCB1 p.Ala155Val 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-ser969 (accessed [today's date]).

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