Is PLCB3 p.Ser767Pro (c.2299T>C) pathogenic?

PLCB3 p.Ser767Pro (c.2299T>C) is classified Uncertain significance in PLCB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely pathogenic (0.8228); Absent from gnomAD v4.1.

How common is PLCB3 p.Ser767Pro (c.2299T>C) in the general population?

PLCB3 p.Ser767Pro (c.2299T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLCB3 p.Ser767Pro (c.2299T>C)?

AlphaMissense predicts likely pathogenic (score 0.8228) — an in-silico prediction, not a clinical call.

PLCB3 p.Ser767Pro

c.2299T>C · VCV3419959

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8228 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8228	likely pathogenic
REVEL	0.466	indeterminate
SaProt	LLR -8.90	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 5.1	GERP 2, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 3,869 bp · p 2e-18 · regional, not allelic
Overall
CADD	28.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLCB3
Protein: p.Ser767Pro
Coding: c.2299T>C
MANE Select: NM_000932
Type: single nucleotide variant
Location: chr11:64262752 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.47 · 13 PDB
Residue 767: an α-helix; the c2 domain

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

Similar variants

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
PLCB3 p.Thr158Met Likely 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-ser767pro (accessed [today's date]).

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