Is PLCB4 p.Asp360Val (c.1079A>T) pathogenic?

PLCB4 p.Asp360Val (c.1079A>T) is classified Pathogenic in PLCB4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-03-01). AlphaMissense: likely pathogenic (1); No allele count reported in gnomAD v4.1 (AN 1,583,288); Associated with auriculocondylar syndrome 2.

What condition is associated with PLCB4 p.Asp360Val (c.1079A>T)?

PLCB4 p.Asp360Val (c.1079A>T) is associated with auriculocondylar syndrome 2 (ClinVar).

How common is PLCB4 p.Asp360Val (c.1079A>T) in the general population?

PLCB4 p.Asp360Val (c.1079A>T) is no allele count reported in gnomAD v4.1 (AN 1,583,288) (gnomAD).

What do computational predictors say about PLCB4 p.Asp360Val (c.1079A>T)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

PLCB4 p.Asp360Val

c.1079A>T · rs397514771 · VCV64695

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,583,288)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

auriculocondylar syndrome 2

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic ✓ concordant with ClinVar · top 2% in PLCB4
REVEL	0.774	moderately pathogenic-leaning
SaProt	LLR -15.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 25 kb · p 4.1e-14 · regional, not allelic
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,583,288). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PLCB4
Protein: p.Asp360Val
Coding: c.1079A>T
MANE Select: NM_001377142
dbSNP: rs397514771
Type: single nucleotide variant
Location: chr20:9387477 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 86.03
Residue 360: the pi-plc x-box domain; a UniProt-annotated variant site (in arcnd2a; likely pathogenic); a UniProt-annotated variant site (in arcnd2a; likely pathogenic; decreased function in phospholipase c-activating endothelin receptor signaling pathway; dominant negative effect; no effect on localization to cell membrane)

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.Asp360Glu Likely pathogenic ★ same residue
PLCB4 p.Asp360Asn Pathogenic same residue
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

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-asp360val (accessed [today's date]).

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