Is PRKD2 p.Pro608Ala (c.1822C>G) pathogenic?

PRKD2 p.Pro608Ala (c.1822C>G) is classified Uncertain significance in PRKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0637); Absent from gnomAD v4.1.

How common is PRKD2 p.Pro608Ala (c.1822C>G) in the general population?

PRKD2 p.Pro608Ala (c.1822C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKD2 p.Pro608Ala (c.1822C>G)?

AlphaMissense predicts likely benign (score 0.0637) — an in-silico prediction, not a clinical call.

PRKD2 p.Pro608Ala

c.1822C>G · VCV4144515

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0637 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0637	likely benign
REVEL	0.467	indeterminate
SaProt	LLR -11.28	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.2	GERP 0.78, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 16 kb · p 2.2e-27 · regional, not allelic
Overall
CADD	19.18	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: PRKD2
Protein: p.Pro608Ala
Coding: c.1822C>G
MANE Select: NM_016457
Type: single nucleotide variant
Location: chr19:46689686 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 608: the protein kinase domain

Full PRKD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PKD2 p.Phe608Leu Uncertain significance ★★ ⚠ same residue
PRKD2 p.Pro608= Benign ★★ same residue
PKD2 c.1094+1G>A Pathogenic ★★ same type
PKD2 c.1094+1G>C Pathogenic ★★ same type
PKD2 c.1319+1G>A Pathogenic/Likely pathogenic ★★ same type
PKD2 c.1320-2A>C Pathogenic/Likely pathogenic ★★ same type
PKD2 c.1548+1G>A Pathogenic/Likely pathogenic ★★ same type
PKD2 c.1549-1G>A Pathogenic/Likely pathogenic ★★ 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/prkd2-p-pro608ala (accessed [today's date]).

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