Is PRKCE p.Phe511Leu (c.1533C>G) pathogenic?

PRKCE p.Phe511Leu (c.1533C>G) is classified Uncertain significance in PRKCE (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-02). AlphaMissense: likely pathogenic (0.9995); Very rare (popmax 0.00167%, amr).

How common is PRKCE p.Phe511Leu (c.1533C>G) in the general population?

PRKCE p.Phe511Leu (c.1533C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PRKCE p.Phe511Leu (c.1533C>G)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

PRKCE p.Phe511Leu

c.1533C>G · rs765421914 · VCV931705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 10% in PRKCE
REVEL	0.52	indeterminate
SaProt	LLR -12.55	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 79 kb · p 1.6e-07 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000688% 11/1,599,608 alleles · very rare exomes 10/1,447,400 · genomes 1/152,208 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,400
European (non-Finnish)	0.000763%	131,106

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: PRKCE
Protein: p.Phe511Leu
Coding: c.1533C>G
MANE Select: NM_005400
dbSNP: rs765421914
Type: single nucleotide variant
Location: chr2:46086303 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.45 · 2 PDB
Residue 511: the protein kinase domain

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

Similar variants

PRKCE p.Phe511Cys Uncertain significance ★ ⚠ same residue
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

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-phe511leu (accessed [today's date]).

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