Is PRKD1 p.Pro545Ser (c.1633C>T) pathogenic?

PRKD1 p.Pro545Ser (c.1633C>T) is classified Uncertain significance in PRKD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-08). AlphaMissense: likely benign (0.1107); Absent from gnomAD v4.1; Associated with PRKD1-related disorder.

What condition is associated with PRKD1 p.Pro545Ser (c.1633C>T)?

PRKD1 p.Pro545Ser (c.1633C>T) is associated with PRKD1-related disorder (ClinVar).

How common is PRKD1 p.Pro545Ser (c.1633C>T) in the general population?

PRKD1 p.Pro545Ser (c.1633C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKD1 p.Pro545Ser (c.1633C>T)?

AlphaMissense predicts likely benign (score 0.1107) — an in-silico prediction, not a clinical call.

PRKD1 p.Pro545Ser

c.1633C>T · rs2502557348 · VCV2628732

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1107 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PRKD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1107	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.75	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 5.8	GERP 0.75, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 86 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	16.04	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

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: PRKD1
Protein: p.Pro545Ser
Coding: c.1633C>T
MANE Select: NM_002742
dbSNP: rs2502557348
Type: single nucleotide variant
Location: chr14:29630781 (GRCh38)
Gene constraint: LOEUF 0.762 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.99

Full PRKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PRKD1-related disorder

Similar variants

PRKD1 p.Tyr252His Uncertain significance ★★ ⚠ same condition
PRKD1 p.Ala21Pro Uncertain significance ★ ⚠ same condition
PRKD1 p.Lys268Ter Uncertain significance ★ same condition
PRKD1 p.Gln297Arg Uncertain significance ⚠ same condition
PRKD1 p.Gln537Ter Uncertain significance same condition
PRKD1 p.Ala873= Likely benign same condition
PRKD1 p.Glu646= Likely benign same condition
PRKD1 p.Pro314= Benign same condition

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/prkd1-p-pro545ser (accessed [today's date]).

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