Is PRKD3 p.Ser142Ala (c.424T>G) pathogenic?

PRKD3 p.Ser142Ala (c.424T>G) is classified Uncertain significance in PRKD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: ambiguous (0.4454); Absent from gnomAD v4.1.

How common is PRKD3 p.Ser142Ala (c.424T>G) in the general population?

PRKD3 p.Ser142Ala (c.424T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKD3 p.Ser142Ala (c.424T>G)?

AlphaMissense predicts ambiguous (score 0.4454) — an in-silico prediction, not a clinical call.

PRKD3 p.Ser142Ala

c.424T>G · VCV4572117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4454 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4454	ambiguous
REVEL	0.47	indeterminate
SaProt	LLR -9.94	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 47 kb · p 0.51 · regional, not allelic
Overall
CADD	24.0	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: PRKD3
Protein: p.Ser142Ala
Coding: c.424T>G
MANE Select: NM_005813
Type: single nucleotide variant
Location: chr2:37293136 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.57 · 1 PDB

Full PRKD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRKD3 p.Ala3Ser Uncertain significance ★ ⚠ same type
PRKD3 p.Ala511Gly Uncertain significance ★ ⚠ same type
PRKD3 p.Ala530Gly Uncertain significance ★ ⚠ same type
PRKD3 p.Arg211His Uncertain significance ★ ⚠ same type
PRKD3 p.Arg211Leu Uncertain significance ★ ⚠ same type
PRKD3 p.Arg297Cys Uncertain significance ★ ⚠ same type
PRKD3 p.Arg355Gln Uncertain significance ★ ⚠ same type
PRKD3 p.Arg429Met 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/prkd3-p-ser142ala (accessed [today's date]).

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