Is PLCB3 p.Pro6Leu (c.17C>T) pathogenic?

PLCB3 p.Pro6Leu (c.17C>T) is classified Uncertain significance in PLCB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-14). AlphaMissense: ambiguous (0.3557); Very rare (popmax 0.00147%, afr).

How common is PLCB3 p.Pro6Leu (c.17C>T) in the general population?

PLCB3 p.Pro6Leu (c.17C>T) is very rare (popmax 0.00147%, afr) (gnomAD).

What do computational predictors say about PLCB3 p.Pro6Leu (c.17C>T)?

AlphaMissense predicts ambiguous (score 0.3557) — an in-silico prediction, not a clinical call.

PLCB3 p.Pro6Leu

c.17C>T · rs769667107 · VCV2209532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3557 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00147%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3557	ambiguous
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.26	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 5,066 bp · p 7.7e-11 · regional, not allelic
Overall
CADD	27.4	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

Grpmax group 0.00147% African / African-American · 1/68,188 alleles

Filtering AF 0.00031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000224%

Overall 0.000611% 9/1,472,948 alleles · very rare exomes 5/1,321,078 · genomes 4/151,870 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00147%	68,188
European (non-Finnish)	0.000722%	138,599

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: PLCB3
Protein: p.Pro6Leu
Coding: c.17C>T
MANE Select: NM_000932
dbSNP: rs769667107
Type: single nucleotide variant
Location: chr11:64251666 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.47 · 13 PDB

Full PLCB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLCB3 p.Ser1107Leu Uncertain significance ★★ ⚠ same type
PLCB3 c.2038+7C>A Benign ★★ same type
PLCB3 c.99+8C>T Benign ★★ same type
PLCB3 p.Glu1023Asp Benign ★★ same type
PLCB3 p.Glu60= Benign ★★ same type
PLCB3 p.Pro171= Benign ★★ same type
PLCB3 p.Ser845Leu Benign ★★ same type
PLCB3 p.Thr158Met Likely benign ★★ same type

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/plcb3-p-pro6leu (accessed [today's date]).

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