Is PLCB4 p.Pro800= (c.2400G>A) pathogenic?

PLCB4 p.Pro800= (c.2400G>A) is classified Benign in PLCB4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-18). Common (popmax 9.65%, amr) — too common for a highly-penetrant pathogenic allele; Associated with auriculocondylar syndrome 2.

What condition is associated with PLCB4 p.Pro800= (c.2400G>A)?

PLCB4 p.Pro800= (c.2400G>A) is associated with auriculocondylar syndrome 2 (ClinVar).

PLCB4 p.Pro800=

Q: How common is PLCB4 p.Pro800= (c.2400G>A) in the general population?

PLCB4 p.Pro800= (c.2400G>A) is common (popmax 9.65%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2400G>A · rs16995899 · VCV339577

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 9.65%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

auriculocondylar syndrome 2

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 -9.8	GERP -4.7
Overall
CADD	1.362	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.65% Admixed American · 5,785/59,944 alleles

Filtering AF 9.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.36%

Overall 0.584% 9,430/1,613,820 alleles · common exomes 8,051/1,461,554 · genomes 1,379/152,266 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	9.65%	10
East Asian	4.84%	21
Ashkenazi Jewishnot grpmax-eligible	0.75%	133
Remaining individualsnot grpmax-eligible	0.53%	189
Finnishnot grpmax-eligible	0.342%	292
South Asian	0.142%	706
African / African-American	0.125%	798
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.0403%	2,484

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: PLCB4
Protein: p.Pro800=
Coding: c.2400G>A
MANE Select: NM_001377142
dbSNP: rs16995899
Type: single nucleotide variant
Location: chr20:9423828 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 86.03
Residue 800: the c2 domain

Full PLCB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

auriculocondylar syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLCB4 p.Arg633Cys Pathogenic ★★ same condition
PLCB4 p.Arg633His Pathogenic ★★ same condition
PLCB4 p.Asp642Asn Pathogenic/Likely pathogenic ★★ same condition
PLCB4 c.1323+8T>C Uncertain significance ★★ same condition
PLCB4 c.*586C>T Uncertain significance ★★ same condition
PLCB4 p.Met965Thr Uncertain significance ★★ ⚠ same condition
PLCB4 c.1065-8A>G Benign ★★ same condition
PLCB4 c.1611+12C>T Likely benign ★★ 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/plcb4-p-pro800 (accessed [today's date]).

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