Is PKDCC p.Arg185Pro (c.554G>C) pathogenic?

PKDCC p.Arg185Pro (c.554G>C) is classified Uncertain significance in PKDCC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.1404); No allele count reported in gnomAD v4.1 (AN 1,582,378); Associated with Inborn genetic diseases.

What condition is associated with PKDCC p.Arg185Pro (c.554G>C)?

PKDCC p.Arg185Pro (c.554G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PKDCC p.Arg185Pro (c.554G>C) in the general population?

PKDCC p.Arg185Pro (c.554G>C) is no allele count reported in gnomAD v4.1 (AN 1,582,378) (gnomAD).

What do computational predictors say about PKDCC p.Arg185Pro (c.554G>C)?

AlphaMissense predicts likely benign (score 0.1404) — an in-silico prediction, not a clinical call.

PKDCC p.Arg185Pro

c.554G>C · VCV3933055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1404 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,582,378)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1404	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.68	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 12	GERP 0.82, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 9,485 bp · p 0.012 · regional, not allelic
Overall
CADD	22.3	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

No allele count reported in gnomAD v4.1 (AN 1,582,378). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PKDCC
Protein: p.Arg185Pro
Coding: c.554G>C
MANE Select: NM_138370
Type: single nucleotide variant
Location: chr2:42048753 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.96
Residue 185: the protein kinase domain

Full PKDCC 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

PKDCC p.Ala299Thr Uncertain significance ★★ ⚠ same condition
PKDCC p.Arg280Cys Uncertain significance ★★ ⚠ same condition
PKDCC p.Arg338Gln Uncertain significance ★★ ⚠ same condition
PKDCC p.Arg393Gln Uncertain significance ★★ ⚠ same condition
PKDCC p.Asp295Glu Uncertain significance ★★ ⚠ same condition
PKDCC p.Asp89His Uncertain significance ★★ ⚠ same condition
PKDCC p.Cys331Arg Uncertain significance ★★ ⚠ same condition
PKDCC p.Glu380Lys 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/pkdcc-p-arg185pro (accessed [today's date]).

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