Is PKD1 p.Pro137= (c.411G>A) pathogenic?

PKD1 p.Pro137= (c.411G>A) is classified Likely benign in PKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-02). Ultra-rare (popmax 0.0515%, eas); Associated with polycystic kidney disease 1.

What condition is associated with PKD1 p.Pro137= (c.411G>A)?

PKD1 p.Pro137= (c.411G>A) is associated with polycystic kidney disease 1 (ClinVar).

How common is PKD1 p.Pro137= (c.411G>A) in the general population?

PKD1 p.Pro137= (c.411G>A) is ultra-rare (popmax 0.0515%, eas) (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.Pro137=

c.411G>A · VCV3780257

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0515%, eas)

Conditions

polycystic kidney disease 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.7	GERP -2.2
Overall
CADD	3.772	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0515% East Asian · 23/44,634 alleles

Filtering AF 0.0352% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0298%

Overall 0.00213% 33/1,549,948 alleles · ultra-rare exomes 29/1,397,688 · genomes 4/152,260 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0515%	1,941
South Asian	0.00781%	12,809
Remaining individualsnot grpmax-eligible	0.00165%	60,584
European (non-Finnish)	0.000176%	569,282

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.Pro137=
Coding: c.411G>A
MANE Select: NM_001009944
Type: single nucleotide variant
Location: chr16:2118794 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 137: the lrrct domain

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.Pro137Leu Likely benign 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
PKD1 c.11269+1G>C 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-pro137 (accessed [today's date]).

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