Is PLCB1 p.Pro983Ser (c.2947C>T) pathogenic?

PLCB1 p.Pro983Ser (c.2947C>T) is classified Uncertain significance in PLCB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-12). AlphaMissense: likely benign (0.0757); Very rare (popmax 0.00662%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PLCB1 p.Pro983Ser (c.2947C>T)?

PLCB1 p.Pro983Ser (c.2947C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 12 (ClinVar).

How common is PLCB1 p.Pro983Ser (c.2947C>T) in the general population?

PLCB1 p.Pro983Ser (c.2947C>T) is very rare (popmax 0.00662%, nfe) (gnomAD).

What do computational predictors say about PLCB1 p.Pro983Ser (c.2947C>T)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

PLCB1 p.Pro983Ser

c.2947C>T · rs371547145 · VCV410074

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00662%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 140 kb · p 0.025 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00662% European (non-Finnish) · 78/1,178,316 alleles

Filtering AF 0.00539% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00509% 82/1,611,570 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00662%	15,107
Remaining individualsnot grpmax-eligible	0.00481%	20,789
African / African-American	0.00134%	74,878

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.Pro983Ser
Coding: c.2947C>T
MANE Select: NM_015192
dbSNP: rs371547145
Type: single nucleotide variant
Location: chr20:8774555 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 983: 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.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
PLCB1 p.Ala1116Val Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala1182Val Uncertain significance ★★ ⚠ same condition
PLCB1 p.Ala155Val 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-pro983ser (accessed [today's date]).

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