Is DNAJB11 p.Pro54Arg (c.161C>G) pathogenic?

DNAJB11 p.Pro54Arg (c.161C>G) is classified Likely pathogenic in DNAJB11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-30). AlphaMissense: likely pathogenic (0.9852); Absent from gnomAD v4.1; Associated with autosomal dominant polycystic kidney disease.

What condition is associated with DNAJB11 p.Pro54Arg (c.161C>G)?

DNAJB11 p.Pro54Arg (c.161C>G) is associated with autosomal dominant polycystic kidney disease, polycystic kidney disease 6 with or without polycystic liver disease (ClinVar).

How common is DNAJB11 p.Pro54Arg (c.161C>G) in the general population?

DNAJB11 p.Pro54Arg (c.161C>G) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal dominant polycystic kidney disease inherited?

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

What do computational predictors say about DNAJB11 p.Pro54Arg (c.161C>G)?

AlphaMissense predicts likely pathogenic (score 0.9852) — an in-silico prediction, not a clinical call.

DNAJB11 p.Pro54Arg

c.161C>G · rs1553849919 · VCV549847

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant polycystic kidney disease

Computational evidence

Protein change
AlphaMissense	0.9852	likely pathogenic ✓ concordant with ClinVar · top 10% in DNAJB11
REVEL	0.94	strongly pathogenic-leaning
SaProt	LLR -17.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 15 kb · p 7.3e-05 · regional, not allelic
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAJB11
Protein: p.Pro54Arg
Coding: c.161C>G
MANE Select: NM_016306
dbSNP: rs1553849919
Type: single nucleotide variant
Location: chr3:186572187 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.34
Residue 54: the j domain; a UniProt-annotated variant site (in pkd6)

Full DNAJB11 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

Also linked: polycystic kidney disease 6 with or without polycystic liver disease

For Autosomal dominant polycystic kidney disease (Orphanet):

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

Similar variants

DNAJB11 p.Arg206Ter Pathogenic ★★ same condition
DNAJB11 p.Arg242Ter Pathogenic ★★ same condition
DNAJB11 p.Arg24Ter Pathogenic ★★ same condition
DNAJB11 p.Arg34Ter Pathogenic ★★ same condition
DNAJB11 p.Glu144Ter Pathogenic/Likely pathogenic ★★ same condition
DNAJB11 p.Leu77Pro Likely pathogenic ★★ same condition
DNAJB11 p.Asp55Asn Uncertain significance ★★ ⚠ same condition
DNAJB11 c.324-1G>A 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/dnajb11-p-pro54arg (accessed [today's date]).

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