Is PLCB1 p.Ser982Arg (c.2946C>G) pathogenic?

PLCB1 p.Ser982Arg (c.2946C>G) is classified Uncertain significance in PLCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: ambiguous (0.434); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PLCB1 p.Ser982Arg (c.2946C>G)?

PLCB1 p.Ser982Arg (c.2946C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PLCB1 p.Ser982Arg (c.2946C>G) in the general population?

PLCB1 p.Ser982Arg (c.2946C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLCB1 p.Ser982Arg (c.2946C>G)?

AlphaMissense predicts ambiguous (score 0.434) — an in-silico prediction, not a clinical call.

PLCB1 p.Ser982Arg

c.2946C>G · rs369387650 · VCV3214373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.434 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.434	ambiguous
REVEL	0.192	benign-leaning
SaProt	LLR -8.71	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.18	GERP -2.9, phastCons 0.97
Regional constraint	o/e 0.89	unconstrained · MANE · 140 kb · p 0.025 · regional, not allelic
Overall
CADD	15.43	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: PLCB1
Protein: p.Ser982Arg
Coding: c.2946C>G
MANE Select: NM_015192
dbSNP: rs369387650
Type: single nucleotide variant
Location: chr20:8774554 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 982: 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

Similar variants

PLCB1 p.Ser982= Likely benign ★ same residue
PLCB1 p.Ala1046Ser Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala1182Val Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala155Val Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala78Thr Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala890Val Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala970Thr Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala995Thr 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-ser982arg (accessed [today's date]).

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