Is PKN2 p.Phe607Ser (c.1820T>C) pathogenic?

PKN2 p.Phe607Ser (c.1820T>C) is classified Uncertain significance in PKN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely benign (0.0715); Ultra-rare (popmax 0.027%, eas).

How common is PKN2 p.Phe607Ser (c.1820T>C) in the general population?

PKN2 p.Phe607Ser (c.1820T>C) is ultra-rare (popmax 0.027%, eas) (gnomAD).

What do computational predictors say about PKN2 p.Phe607Ser (c.1820T>C)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

PKN2 p.Phe607Ser

c.1820T>C · rs769594034 · VCV3213938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -3.89	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 8,107 bp · p 0.021 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 0.027% East Asian · 12/44,456 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0122%

Overall 0.00102% 16/1,572,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.027%	3,705
Remaining individualsnot grpmax-eligible	0.00164%	60,888
European (non-Finnish)	0.000261%	383,821

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: PKN2
Protein: p.Phe607Ser
Coding: c.1820T>C
MANE Select: NM_006256
dbSNP: rs769594034
Type: single nucleotide variant
Location: chr1:88807329 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.06 · 4 PDB

Full PKN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PKN2 p.Ala30Thr Uncertain significance ★ ⚠ same type
PKN2 p.Ala355Pro Uncertain significance ★ ⚠ same type
PKN2 p.Ala923Thr Uncertain significance ★ ⚠ same type
PKN2 p.Arg130His Uncertain significance ★ ⚠ same type
PKN2 p.Arg130Leu Uncertain significance ★ ⚠ same type
PKN2 p.Arg20Gln Uncertain significance ★ ⚠ same type
PKN2 p.Arg223Lys Uncertain significance ★ ⚠ same type
PKN2 p.Arg223Ser 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/pkn2-p-phe607ser (accessed [today's date]).

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