Is PRKCD p.Pro49Gln (c.146C>A) pathogenic?

PRKCD p.Pro49Gln (c.146C>A) is classified Uncertain significance in PRKCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: ambiguous (0.4248); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PRKCD p.Pro49Gln (c.146C>A)?

PRKCD p.Pro49Gln (c.146C>A) is associated with Inborn genetic diseases (ClinVar).

How common is PRKCD p.Pro49Gln (c.146C>A) in the general population?

PRKCD p.Pro49Gln (c.146C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKCD p.Pro49Gln (c.146C>A)?

AlphaMissense predicts ambiguous (score 0.4248) — an in-silico prediction, not a clinical call.

PRKCD p.Pro49Gln

c.146C>A · VCV3783330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4248 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4248	ambiguous
REVEL	0.505	indeterminate
SaProt	LLR -10.72	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 3,131 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	27.5	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: PRKCD
Protein: p.Pro49Gln
Coding: c.146C>A
MANE Select: NM_006254
Type: single nucleotide variant
Location: chr3:53179607 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 49: the c2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRKCD p.Pro49= Likely benign ★ same residue
PRKCD p.Ala195Val Uncertain significance ★★ ⚠ same condition
PRKCD p.Ala404Gly Uncertain significance ★★ ⚠ same condition
PRKCD p.Ala454Thr Uncertain significance ★★ same condition
PRKCD p.Arg273Trp Uncertain significance ★★ ⚠ same condition
PRKCD p.Arg40His Uncertain significance ★★ same condition
PRKCD p.Arg444Cys Uncertain significance ★★ same condition
PRKCD p.Arg561His Uncertain significance ★★ 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/prkcd-p-pro49gln (accessed [today's date]).

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