Is DZIP1L p.Arg339= (c.1017A>G) pathogenic?

DZIP1L p.Arg339= (c.1017A>G) is classified Likely benign in DZIP1L (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-12). Ultra-rare (popmax 0.0442%, nfe); Associated with polycystic kidney disease 5.

What condition is associated with DZIP1L p.Arg339= (c.1017A>G)?

DZIP1L p.Arg339= (c.1017A>G) is associated with polycystic kidney disease 5 (ClinVar).

How common is DZIP1L p.Arg339= (c.1017A>G) in the general population?

DZIP1L p.Arg339= (c.1017A>G) is ultra-rare (popmax 0.0442%, nfe) (gnomAD).

How is Autosomal recessive polycystic kidney disease inherited?

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

DZIP1L p.Arg339=

c.1017A>G · rs147201722 · VCV721269

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0442%, nfe)

Conditions

polycystic kidney disease 5

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 -0.64	GERP -3.4, phastCons 0.031
Overall
CADD	5.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0442% European (non-Finnish) · 522/1,180,012 alleles

Filtering AF 0.0411% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0399%

Overall 0.0337% 544/1,614,160 alleles · ultra-rare exomes 519/1,461,828 · genomes 25/152,332 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0442%	2,261
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Admixed American	0.00666%	15,004
African / African-American	0.00533%	18,761
Finnishnot grpmax-eligible	0.00312%	32,021
South Asian	0.0011%	91,082

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: DZIP1L
Protein: p.Arg339=
Coding: c.1017A>G
MANE Select: NM_173543
dbSNP: rs147201722
Type: single nucleotide variant
Location: chr3:138087006 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.03
Residue 339: a UniProt-annotated variant site (in pkd5)

Full DZIP1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polycystic kidney disease 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive polycystic kidney disease (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Germany)

Similar variants

DZIP1L p.Gly609Arg Uncertain significance ★★ ⚠ same condition
DZIP1L p.Arg321Trp Benign ★★ ⚠ same condition
DZIP1L p.Arg593His Benign ★★ same condition
DZIP1L p.Lys645Glu Benign ★★ same condition
DZIP1L p.Thr545Ala Benign ★★ same condition
DZIP1L p.Gln155Ter Pathogenic ★ same condition
DZIP1L p.Gln243Ter Likely pathogenic ★ same condition
DZIP1L p.Gln524Ter 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/dzip1l-p-arg339 (accessed [today's date]).

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