Is PRKCB p.Thr340Pro (c.1018A>C) pathogenic?

PRKCB p.Thr340Pro (c.1018A>C) is classified Uncertain significance in PRKCB (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-21). AlphaMissense: likely benign (0.2153); Very rare (popmax 0.005%, amr).

How common is PRKCB p.Thr340Pro (c.1018A>C) in the general population?

PRKCB p.Thr340Pro (c.1018A>C) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about PRKCB p.Thr340Pro (c.1018A>C)?

AlphaMissense predicts likely benign (score 0.2153) — an in-silico prediction, not a clinical call.

PRKCB p.Thr340Pro

c.1018A>C · VCV3356712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2153	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -11.72	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 42 kb · p 0.32 · regional, not allelic
Overall
CADD	26.1	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

Grpmax group 0.005% Admixed American · 3/60,018 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,461,870 alleles · very rare

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: PRKCB
Protein: p.Thr340Pro
Coding: c.1018A>C
MANE Select: NM_002738
Type: single nucleotide variant
Location: chr16:24123934 (GRCh38)
Gene constraint: LOEUF 0.241 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.95 · 8 PDB
Residue 340: an α-helix

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

Similar variants

PRKCB c.1395-4A>G Benign ★★ same type
PRKCB p.Ile174= Benign ★★ same type
PRKCB p.Lys29= Benign/Likely benign ★★ same type
PRKCB p.Pro400= Likely benign ★★ same type
PRKCB p.Ala2Pro Uncertain significance ★ ⚠ same type
PRKCB p.Ala395Thr Uncertain significance ★ ⚠ same type
PRKCB p.Ala539Thr Uncertain significance ★ ⚠ same type
PRKCB p.Ala6Thr 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/prkcb-p-thr340pro (accessed [today's date]).

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