Is PKDCC p.Pro103Arg (c.308C>G) pathogenic?

PKDCC p.Pro103Arg (c.308C>G) is classified Uncertain significance in PKDCC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-08). AlphaMissense: likely benign (0.0648); Ultra-rare (popmax 0.0377%, mid); Associated with Inborn genetic diseases.

What condition is associated with PKDCC p.Pro103Arg (c.308C>G)?

PKDCC p.Pro103Arg (c.308C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PKDCC p.Pro103Arg (c.308C>G) in the general population?

PKDCC p.Pro103Arg (c.308C>G) is ultra-rare (popmax 0.0377%, mid) (gnomAD).

What do computational predictors say about PKDCC p.Pro103Arg (c.308C>G)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

PKDCC p.Pro103Arg

c.308C>G · rs1000563945 · VCV1989157

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0377%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.99	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 2	GERP -0.62, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 9,485 bp · p 0.012 · regional, not allelic
Overall
CADD	15.39	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 0.0377% Middle Eastern · 1/2,654 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0124% 138/1,117,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0377%	2,654
Remaining individualsnot grpmax-eligible	0.016%	6,269
European (non-Finnish)	0.0137%	7,290
Admixed American	0.0104%	9,608
African / African-American	0.005%	19,985

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: PKDCC
Protein: p.Pro103Arg
Coding: c.308C>G
MANE Select: NM_138370
dbSNP: rs1000563945
Type: single nucleotide variant
Location: chr2:42048507 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.96
Residue 103: the 'disordered' region

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-pro103arg (accessed [today's date]).

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