Is PLCB3 p.Ala189Val (c.566C>T) pathogenic?

PLCB3 p.Ala189Val (c.566C>T) is classified Uncertain significance in PLCB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely pathogenic (0.7859); Very rare (popmax 0.00508%, eas).

How common is PLCB3 p.Ala189Val (c.566C>T) in the general population?

PLCB3 p.Ala189Val (c.566C>T) is very rare (popmax 0.00508%, eas) (gnomAD).

What do computational predictors say about PLCB3 p.Ala189Val (c.566C>T)?

AlphaMissense predicts likely pathogenic (score 0.7859) — an in-silico prediction, not a clinical call.

PLCB3 p.Ala189Val

c.566C>T · rs771762676 · VCV3214402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00508%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7859	likely pathogenic
REVEL	0.322	indeterminate
SaProt	LLR -9.76	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 5,066 bp · p 7.7e-11 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00508% East Asian · 2/39,360 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0012%

Overall 0.00207% 32/1,543,812 alleles · very rare exomes 31/1,395,556 · genomes 1/148,256 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00508%	19,680
Ashkenazi Jewishnot grpmax-eligible	0.00368%	27,208
Remaining individualsnot grpmax-eligible	0.00344%	29,094
South Asian	0.00222%	45,026
European (non-Finnish)	0.00211%	47,371
African / African-American	0.00138%	72,350

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: PLCB3
Protein: p.Ala189Val
Coding: c.566C>T
MANE Select: NM_000932
dbSNP: rs771762676
Type: single nucleotide variant
Location: chr11:64255585 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.47 · 13 PDB
Residue 189: an α-helix

Full PLCB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLCB3 p.Ala189Ser Uncertain significance ★ ⚠ same residue
PLCB3 p.Ser1107Leu Uncertain significance ★★ ⚠ same type
PLCB3 c.2038+7C>A Benign ★★ same type
PLCB3 c.99+8C>T Benign ★★ same type
PLCB3 p.Glu1023Asp Benign ★★ same type
PLCB3 p.Glu60= Benign ★★ same type
PLCB3 p.Pro171= Benign ★★ same type
PLCB3 p.Ser845Leu Benign ★★ same type

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/plcb3-p-ala189val (accessed [today's date]).

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