Is PLCB4 p.Asp876= (c.2628C>T) pathogenic?

PLCB4 p.Asp876= (c.2628C>T) is classified Benign/Likely benign in PLCB4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-03-18). Rare (popmax 0.905%, afr); Associated with auriculocondylar syndrome 2.

What condition is associated with PLCB4 p.Asp876= (c.2628C>T)?

PLCB4 p.Asp876= (c.2628C>T) is associated with auriculocondylar syndrome 2 (ClinVar).

How common is PLCB4 p.Asp876= (c.2628C>T) in the general population?

PLCB4 p.Asp876= (c.2628C>T) is rare (popmax 0.905%, afr) (gnomAD).

PLCB4 p.Asp876=

c.2628C>T · rs35218589 · VCV339580

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.905%, afr)

Conditions

auriculocondylar syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.87	GERP -5.2, phastCons 0.012
Overall
CADD	7.596	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.905% African / African-American · 679/75,014 alleles

Filtering AF 0.849% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.826%

Overall 0.0492% 794/1,613,916 alleles · rare exomes 364/1,461,688 · genomes 430/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.905%	110
Remaining individualsnot grpmax-eligible	0.0688%	1,454
Middle Eastern	0.066%	1,516
Admixed American	0.06%	1,666
East Asian	0.0178%	5,608
South Asian	0.00988%	10,117
Finnishnot grpmax-eligible	0.00156%	64,018
European (non-Finnish)	0.00119%	84,279

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.Asp876=
Coding: c.2628C>T
MANE Select: NM_001377142
dbSNP: rs35218589
Type: single nucleotide variant
Location: chr20:9437016 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 86.03
Residue 876: 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.Asp876Tyr Uncertain significance ★ ⚠ 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
PLCB4 c.1065-8A>G 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-asp876 (accessed [today's date]).

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