Is PRKCE p.Asp115His (c.343G>C) pathogenic?

PRKCE p.Asp115His (c.343G>C) is classified Uncertain significance in PRKCE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: ambiguous (0.4819); Absent from gnomAD v4.1.

How common is PRKCE p.Asp115His (c.343G>C) in the general population?

PRKCE p.Asp115His (c.343G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKCE p.Asp115His (c.343G>C)?

AlphaMissense predicts ambiguous (score 0.4819) — an in-silico prediction, not a clinical call.

PRKCE p.Asp115His

c.343G>C · VCV3425125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4819 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4819	ambiguous
REVEL	0.343	indeterminate
SaProt	LLR -10.20	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 191 kb · p 7e-09 · regional, not allelic
Overall
CADD	33.0	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

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.Asp115His
Coding: c.343G>C
MANE Select: NM_005400
Type: single nucleotide variant
Location: chr2:45652443 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.45 · 2 PDB
Residue 115: 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-asp115his (accessed [today's date]).

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