Is PKD1 p.Pro404= (c.1212G>A) pathogenic?

PKD1 p.Pro404= (c.1212G>A) is classified Conflicting classifications of pathogenicity in PKD1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-07). Ultra-rare (popmax 0.0117%, amr); Associated with polycystic kidney disease 1.

What condition is associated with PKD1 p.Pro404= (c.1212G>A)?

PKD1 p.Pro404= (c.1212G>A) is associated with polycystic kidney disease 1 (ClinVar).

How common is PKD1 p.Pro404= (c.1212G>A) in the general population?

PKD1 p.Pro404= (c.1212G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

How is Autosomal dominant polycystic kidney disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PKD1 p.Pro404=

c.1212G>A · rs578104257 · VCV3045000

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

polycystic kidney disease 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.5	GERP -2.6
Overall
CADD	8.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,994 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00267% 43/1,609,908 alleles · ultra-rare exomes 38/1,457,586 · genomes 5/152,322 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,571
African / African-American	0.00667%	14,986
Remaining individualsnot grpmax-eligible	0.00482%	20,747
East Asian	0.00446%	22,436
South Asian	0.0022%	45,480
European (non-Finnish)	0.00204%	49,130

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: PKD1
Protein: p.Pro404=
Coding: c.1212G>A
MANE Select: NM_001009944
dbSNP: rs578104257
Type: single nucleotide variant
Location: chr16:2117662 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full PKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polycystic kidney disease 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant polycystic kidney disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PKD1 p.Pro404Arg Uncertain significance ★★ ⚠ same residue
PKD1 p.Pro404Gln Uncertain significance ★ ⚠ same residue
PKD1 c.10619-2A>G Pathogenic ★★ same condition
PKD1 c.10821+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD1 c.10821+2T>G Pathogenic/Likely pathogenic ★★ same condition
PKD1 c.11017-10C>A Pathogenic/Likely pathogenic ★★ same condition
PKD1 c.11017-25A>C Likely pathogenic ★★ same condition
PKD1 c.11017-25A>G Likely pathogenic ★★ 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/pkd1-p-pro404 (accessed [today's date]).

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