Is PLCB1 p.Asp34= (c.102C>T) pathogenic?

PLCB1 p.Asp34= (c.102C>T) is classified Benign/Likely benign in PLCB1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 22.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with PLCB1 p.Asp34= (c.102C>T)?

PLCB1 p.Asp34= (c.102C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 12 (ClinVar).

PLCB1 p.Asp34=

Q: How common is PLCB1 p.Asp34= (c.102C>T) in the general population?

PLCB1 p.Asp34= (c.102C>T) is common (popmax 22.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.102C>T · rs16994453 · VCV129899

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 22.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.39, phastCons 1
Overall
CADD	14.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.3% African / African-American · 15,670/70,262 alleles

Filtering AF 22% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.9%

Overall 15.3% 218,968/1,427,118 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.3%	4
South Asian	19%	5
East Asian	17.6%	6
Finnishnot grpmax-eligible	16.4%	6
European (non-Finnish)	14.9%	7
Amishnot grpmax-eligible	14.6%	7
Remaining individualsnot grpmax-eligible	14.6%	7
Middle Eastern	11.7%	9
Ashkenazi Jewishnot grpmax-eligible	11.3%	9
Admixed American	9.84%	10

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.Asp34=
Coding: c.102C>T
MANE Select: NM_015192
dbSNP: rs16994453
Type: single nucleotide variant
Location: chr20:8150296 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55

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-asp34 (accessed [today's date]).

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