Is PRKD2 p.Ser710Pro (c.2128T>C) pathogenic?

PRKD2 p.Ser710Pro (c.2128T>C) is classified Uncertain significance in PRKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely pathogenic (0.9993); Very rare (popmax 6.2e-05%).

How common is PRKD2 p.Ser710Pro (c.2128T>C) in the general population?

PRKD2 p.Ser710Pro (c.2128T>C) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about PRKD2 p.Ser710Pro (c.2128T>C)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

PRKD2 p.Ser710Pro

c.2128T>C · VCV3938184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic · top 5% in PRKD2
REVEL	0.643	indeterminate
SaProt	LLR -10.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 0.86, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 16 kb · p 2.2e-27 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 6.2e-05%

Overall 6.2e-05% 1/1,612,860 alleles · very rare exomes 1/1,460,546 · genomes 0/152,314 · 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: PRKD2
Protein: p.Ser710Pro
Coding: c.2128T>C
MANE Select: NM_016457
Type: single nucleotide variant
Location: chr19:46678606 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 710: the protein kinase domain; a modified residue (phosphoserine)

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

Similar variants

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
PKD2 c.1716+2T>A Pathogenic/Likely pathogenic ★★ same type
PKD2 c.1898+1G>A 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-ser710pro (accessed [today's date]).

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