Is PLCB3 p.Ala353Val (c.1058C>T) pathogenic?

PLCB3 p.Ala353Val (c.1058C>T) is classified Likely benign in PLCB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0995); Absent from gnomAD v4.1.

How common is PLCB3 p.Ala353Val (c.1058C>T) in the general population?

PLCB3 p.Ala353Val (c.1058C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLCB3 p.Ala353Val (c.1058C>T)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

PLCB3 p.Ala353Val

c.1058C>T · VCV4568912

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -3.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -1.1	GERP -4
Regional constraint	o/e 0.55	unconstrained · MANE · 2,428 bp · p 2.1e-11 · regional, not allelic
Overall
CADD	9.067	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.Ala353Val
Coding: c.1058C>T
MANE Select: NM_000932
Type: single nucleotide variant
Location: chr11:64258518 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.47 · 13 PDB
Residue 353: the pi-plc x-box domain; an α-helix

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-ala353val (accessed [today's date]).

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