Is PLCB4 p.Asp495= (c.1485C>T) pathogenic?

PLCB4 p.Asp495= (c.1485C>T) is classified Benign/Likely benign in PLCB4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-09). Ultra-rare (popmax 0.1%, sas); Associated with auriculocondylar syndrome 2.

What condition is associated with PLCB4 p.Asp495= (c.1485C>T)?

PLCB4 p.Asp495= (c.1485C>T) is associated with auriculocondylar syndrome 2 (ClinVar).

How common is PLCB4 p.Asp495= (c.1485C>T) in the general population?

PLCB4 p.Asp495= (c.1485C>T) is ultra-rare (popmax 0.1%, sas) (gnomAD).

PLCB4 p.Asp495=

c.1485C>T · rs374048213 · VCV339564

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.1%, sas)

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 -0.15	GERP -4.1, phastCons 0.75
Overall
CADD	9.959	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% South Asian · 91/91,034 alleles

Filtering AF 0.0833% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0771%

Overall 0.0212% 342/1,611,490 alleles · ultra-rare exomes 301/1,459,270 · genomes 41/152,220 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.1%	1,000
Remaining individualsnot grpmax-eligible	0.0272%	3,672
European (non-Finnish)	0.0187%	5,354
Finnishnot grpmax-eligible	0.011%	9,115
African / African-American	0.008%	12,495
Admixed American	0.00167%	60,004

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.Asp495=
Coding: c.1485C>T
MANE Select: NM_001377142
dbSNP: rs374048213
Type: single nucleotide variant
Location: chr20:9395593 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 86.03
Residue 495: the 'disordered' region

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-asp495 (accessed [today's date]).

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