Is PRKCE p.Val3Leu (c.7G>C) pathogenic?

PRKCE p.Val3Leu (c.7G>C) is classified Uncertain significance in PRKCE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.1953); Absent from gnomAD v4.1.

How common is PRKCE p.Val3Leu (c.7G>C) in the general population?

PRKCE p.Val3Leu (c.7G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKCE p.Val3Leu (c.7G>C)?

AlphaMissense predicts likely benign (score 0.1953) — an in-silico prediction, not a clinical call.

PRKCE p.Val3Leu

c.7G>C · rs2465932822 · VCV2479555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1953 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1953	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -7.34	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 8.6	GERP 0.68, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 191 kb · p 7e-09 · regional, not allelic
Overall
CADD	27.9	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: PRKCE
Protein: p.Val3Leu
Coding: c.7G>C
MANE Select: NM_005400
dbSNP: rs2465932822
Type: single nucleotide variant
Location: chr2:45652107 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.45 · 2 PDB
Residue 3: the c2 domain

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

Similar variants

PRKCE p.Ala654Thr Benign ★★ same type
PRKCE p.Lys437= Benign ★★ same type
PRKCE p.Thr455= Benign ★★ same type
PRKCE p.Glu328Gln Likely pathogenic ★ ⚠ same type
PRKCE p.Glu599Lys Pathogenic ★ same type
PRKCE p.Arg150Cys Uncertain significance ★ ⚠ same type
PRKCE p.Arg150His Uncertain significance ★ same type
PRKCE p.Arg152Gln 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/prkce-p-val3leu (accessed [today's date]).

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