Is PLCB4 p.Ser15Phe (c.44C>T) pathogenic?

PLCB4 p.Ser15Phe (c.44C>T) is classified Uncertain significance in PLCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely benign (0.1085); Ultra-rare (popmax 0.0122%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PLCB4 p.Ser15Phe (c.44C>T)?

PLCB4 p.Ser15Phe (c.44C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PLCB4 p.Ser15Phe (c.44C>T) in the general population?

PLCB4 p.Ser15Phe (c.44C>T) is ultra-rare (popmax 0.0122%, nfe) (gnomAD).

What do computational predictors say about PLCB4 p.Ser15Phe (c.44C>T)?

AlphaMissense predicts likely benign (score 0.1085) — an in-silico prediction, not a clinical call.

PLCB4 p.Ser15Phe

c.44C>T · VCV4138642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1085 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1085	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -10.24	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 72 kb · p 0.00011 · regional, not allelic
Overall
CADD	24.8	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 0.0122% European (non-Finnish) · 143/1,168,598 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00991%

Overall 0.00913% 146/1,599,944 alleles · ultra-rare exomes 142/1,447,848 · genomes 4/152,096 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0122%	8,172
Remaining individualsnot grpmax-eligible	0.00323%	30,977
African / African-American	0.00134%	74,732

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.Ser15Phe
Coding: c.44C>T
MANE Select: NM_001377142
Type: single nucleotide variant
Location: chr20:9307858 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 86.03

Full PLCB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLCB4 p.Arg633His Pathogenic ★★ same condition
PLCB4 p.Arg640Gln Uncertain significance ★★ ⚠ same condition
PLCB4 p.Glu1005Lys Uncertain significance ★★ ⚠ same condition
PLCB4 p.Thr1016Met Uncertain significance ★★ ⚠ same condition
PLCB4 p.Val763Ile Uncertain significance ★★ ⚠ same condition
PLCB4 p.Ala1102Thr Uncertain significance ★ ⚠ same condition
PLCB4 p.Ala1102Val Uncertain significance ★ ⚠ same condition
PLCB4 p.Ala21Glu 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-ser15phe (accessed [today's date]).

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