Is PRKD2 p.Pro862Ser (c.2584C>T) pathogenic?

PRKD2 p.Pro862Ser (c.2584C>T) is classified Uncertain significance in PRKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: likely benign (0.0627); Very rare (popmax 0.00669%, amr).

How common is PRKD2 p.Pro862Ser (c.2584C>T) in the general population?

PRKD2 p.Pro862Ser (c.2584C>T) is very rare (popmax 0.00669%, amr) (gnomAD).

What do computational predictors say about PRKD2 p.Pro862Ser (c.2584C>T)?

AlphaMissense predicts likely benign (score 0.0627) — an in-silico prediction, not a clinical call.

PRKD2 p.Pro862Ser

c.2584C>T · rs921682772 · VCV3218830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0627	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.1	GERP -0.93, phastCons 0.88
Regional constraint	o/e 0.90	unconstrained · MANE · 3,896 bp · p 0.24 · regional, not allelic
Overall
CADD	7.292	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 0.00669% Admixed American · 4/59,772 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000622% 10/1,608,834 alleles · very rare exomes 9/1,459,854 · genomes 1/148,980 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00669%	14,943
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,524
Remaining individualsnot grpmax-eligible	0.0016%	62,412
African / African-American	0.00136%	73,790
European (non-Finnish)	0.000254%	392,935

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: PRKD2
Protein: p.Pro862Ser
Coding: c.2584C>T
MANE Select: NM_016457
dbSNP: rs921682772
Type: single nucleotide variant
Location: chr19:46674576 (GRCh38)

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

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-pro862ser (accessed [today's date]).

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