Is PLCB4 p.Val611= (c.1833C>T) pathogenic?

PLCB4 p.Val611= (c.1833C>T) is classified Benign in PLCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.0067%, eas); Associated with auriculocondylar syndrome 2.

What condition is associated with PLCB4 p.Val611= (c.1833C>T)?

PLCB4 p.Val611= (c.1833C>T) is associated with auriculocondylar syndrome 2 (ClinVar).

How common is PLCB4 p.Val611= (c.1833C>T) in the general population?

PLCB4 p.Val611= (c.1833C>T) is very rare (popmax 0.0067%, eas) (gnomAD).

PLCB4 p.Val611=

c.1833C>T · rs778436381 · VCV339569

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

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	all four deltas below 0.2 · C>A here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.7	GERP -4.8
Overall
CADD	4.181	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% East Asian · 3/44,778 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.00195% 31/1,591,124 alleles · very rare exomes 27/1,438,992 · genomes 4/152,132 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0067%	14,926
Remaining individualsnot grpmax-eligible	0.00649%	15,412
Admixed American	0.00501%	19,977
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,422
African / African-American	0.00268%	37,257
European (non-Finnish)	0.00155%	64,421

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.Val611=
Coding: c.1833C>T
MANE Select: NM_001377142
dbSNP: rs778436381
Type: single nucleotide variant
Location: chr20:9408676 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 86.03
Residue 611: the pi-plc y-box 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-val611 (accessed [today's date]).

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