Is PKD2 p.Phe738= (c.2214T>C) pathogenic?

PKD2 p.Phe738= (c.2214T>C) is classified Likely benign in PKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). Very rare (popmax 0.01%, amr); Associated with autosomal dominant polycystic kidney disease.

What condition is associated with PKD2 p.Phe738= (c.2214T>C)?

PKD2 p.Phe738= (c.2214T>C) is associated with autosomal dominant polycystic kidney disease (ClinVar).

How common is PKD2 p.Phe738= (c.2214T>C) in the general population?

PKD2 p.Phe738= (c.2214T>C) is very rare (popmax 0.01%, amr) (gnomAD).

How is Autosomal dominant polycystic kidney disease inherited?

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

PKD2 p.Phe738=

c.2214T>C · rs772819278 · VCV695495

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Conditions

autosomal dominant polycystic kidney disease

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 -1.2	GERP -2.1, phastCons 0.003
Overall
CADD	6.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,022 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000991% 16/1,613,878 alleles · very rare exomes 16/1,461,626 · genomes 0/152,252 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,004
African / African-American	0.00533%	18,756
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000424%	235,953

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: PKD2
Protein: p.Phe738=
Coding: c.2214T>C
MANE Select: NM_000297
dbSNP: rs772819278
Type: single nucleotide variant
Location: chr4:88065469 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 738: the protein kinase domain

Full PKD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant polycystic kidney disease — 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

PKD2 c.1094+1G>A Pathogenic ★★ same condition
PKD2 c.1319+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.1548+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.1898+5G>A Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.2019+1G>A Pathogenic ★★ same condition
PKD2 c.2020-2A>G Likely pathogenic ★★ same condition
PKD2 c.2118+1G>C Pathogenic ★★ same condition
PKD2 c.2522+1G>A Pathogenic/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/pkd2-p-phe738 (accessed [today's date]).

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