Is PRKCB p.Val671Phe (c.2011G>T) pathogenic?

PRKCB p.Val671Phe (c.2011G>T) is classified Uncertain significance in PRKCB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). Very rare (popmax 0.00223%, eas).

How common is PRKCB p.Val671Phe (c.2011G>T) in the general population?

PRKCB p.Val671Phe (c.2011G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

PRKCB p.Val671Phe

c.2011G>T · rs2506810091 · VCV2403281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.127	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 29 kb · p 8.2e-06 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Overall 6.2e-05% 1/1,614,044 alleles · very rare exomes 1/1,461,820 · genomes 0/152,224 · joint denominator

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.Val671Phe
Coding: c.2011G>T
MANE Select: NM_002738
dbSNP: rs2506810091
Type: single nucleotide variant
Location: chr16:24214805 (GRCh38)
Gene constraint: LOEUF 0.241 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.95 · 8 PDB
Residue 671: the agc-kinase c-terminal domain

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-val671phe (accessed [today's date]).

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