Is PLCG1 p.Ser445Phe (c.1334C>T) pathogenic?

PLCG1 p.Ser445Phe (c.1334C>T) is classified Uncertain significance in PLCG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.2017); Absent from gnomAD v4.1.

How common is PLCG1 p.Ser445Phe (c.1334C>T) in the general population?

PLCG1 p.Ser445Phe (c.1334C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLCG1 p.Ser445Phe (c.1334C>T)?

AlphaMissense predicts likely benign (score 0.2017) — an in-silico prediction, not a clinical call.

PLCG1 p.Ser445Phe

c.1334C>T · VCV4568950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2017 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2017	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -8.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -1.4, phastCons 0.99
Regional constraint	o/e 0.70	unconstrained · MANE · 9,622 bp · p 1.1e-21 · regional, not allelic
Overall
CADD	18.64	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLCG1
Protein: p.Ser445Phe
Coding: c.1334C>T
MANE Select: NM_002660
Type: single nucleotide variant
Location: chr20:41165049 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.22 · 6 PDB
Residue 445: the pi-plc x-box domain

Full PLCG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLCG1 p.Arg1277Leu Uncertain significance ★★ ⚠ same type
PLCG1 p.Arg886Cys Uncertain significance ★★ ⚠ same type
PLCG1 p.Asn547Ser Likely benign ★★ same type
PLCG1 p.Asn851= Benign ★★ same type
PLCG1 p.Gly617= Benign ★★ same type
PLCG1 p.Ala1119Asp Uncertain significance ★ ⚠ same type
PLCG1 p.Ala1236Val Uncertain significance ★ ⚠ same type
PLCG1 p.Ala224Thr Uncertain significance ★ ⚠ 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/plcg1-p-ser445phe (accessed [today's date]).

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