Is PLCG2 p.Val1237Leu (c.3709G>C) pathogenic?

PLCG2 p.Val1237Leu (c.3709G>C) is classified Uncertain significance in PLCG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). AlphaMissense: likely benign (0.1208); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PLCG2 p.Val1237Leu (c.3709G>C)?

PLCG2 p.Val1237Leu (c.3709G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PLCG2 p.Val1237Leu (c.3709G>C) in the general population?

PLCG2 p.Val1237Leu (c.3709G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLCG2 p.Val1237Leu (c.3709G>C)?

AlphaMissense predicts likely benign (score 0.1208) — an in-silico prediction, not a clinical call.

PLCG2 p.Val1237Leu

c.3709G>C · rs2507822516 · VCV2311588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1208 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1208	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -5.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.1	GERP 1.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 172 kb · p 0.00029 · regional, not allelic
Overall
CADD	19.01	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: PLCG2
Protein: p.Val1237Leu
Coding: c.3709G>C
MANE Select: NM_002661
dbSNP: rs2507822516
Type: single nucleotide variant
Location: chr16:81956833 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.49 · 8 PDB

Full PLCG2 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

PLCG2 p.Ala11Glu Uncertain significance ★★ ⚠ same condition
PLCG2 p.Arg1187Gln Uncertain significance ★★ ⚠ same condition
PLCG2 p.Arg266His Uncertain significance ★★ ⚠ same condition
PLCG2 p.Arg337Gln Uncertain significance ★★ ⚠ same condition
PLCG2 p.Arg376Gln Uncertain significance ★★ ⚠ same condition
PLCG2 p.Arg589His Uncertain significance ★★ ⚠ same condition
PLCG2 p.Arg956Leu Uncertain significance ★★ ⚠ same condition
PLCG2 p.Asn1225Ile 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/plcg2-p-val1237leu (accessed [today's date]).

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