Is PLCB1 p.Thr989= (c.2967G>A) pathogenic?

PLCB1 p.Thr989= (c.2967G>A) is classified Benign/Likely benign in PLCB1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-05-01). Low-frequency (popmax 2.69%, mid); Associated with Inborn genetic diseases.

What condition is associated with PLCB1 p.Thr989= (c.2967G>A)?

PLCB1 p.Thr989= (c.2967G>A) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 12 (ClinVar).

How common is PLCB1 p.Thr989= (c.2967G>A) in the general population?

PLCB1 p.Thr989= (c.2967G>A) is low-frequency (popmax 2.69%, mid) (gnomAD).

PLCB1 p.Thr989=

c.2967G>A · rs45464693 · VCV129909

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.69%, mid)

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 -2.2	GERP -2.9
Overall
CADD	1.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.69% Middle Eastern · 163/6,058 alleles

Filtering AF 2.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.22%

Overall 0.653% 10,529/1,613,416 alleles · low-frequency exomes 9,451/1,461,154 · genomes 1,078/152,262 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.69%	37
Ashkenazi Jewishnot grpmax-eligible	1.62%	62
African / African-American	0.898%	111
Remaining individualsnot grpmax-eligible	0.839%	119
Admixed American	0.758%	132
European (non-Finnish)	0.666%	150
South Asian	0.344%	291
Finnishnot grpmax-eligible	0.0906%	1,103
East Asian	0.00668%	14,962

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.Thr989=
Coding: c.2967G>A
MANE Select: NM_015192
dbSNP: rs45464693
Type: single nucleotide variant
Location: chr20:8774575 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 989: 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.Thr989Ala Uncertain significance ★ ⚠ same residue
PLCB1 p.Thr989Lys Uncertain significance ★ ⚠ same residue
PLCB1 p.Thr989Met 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

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-thr989 (accessed [today's date]).

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