Is DNAJC5 p.Pro51= (c.153G>T) pathogenic?

DNAJC5 p.Pro51= (c.153G>T) is classified Conflicting classifications of pathogenicity in DNAJC5 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-09-21). Ultra-rare (popmax 0.0219%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Pro51= (c.153G>T)?

DNAJC5 p.Pro51= (c.153G>T) is associated with neuronal ceroid lipofuscinosis, ceroid lipofuscinosis, neuronal, 4 (Kufs type) (ClinVar).

How common is DNAJC5 p.Pro51= (c.153G>T) in the general population?

DNAJC5 p.Pro51= (c.153G>T) is ultra-rare (popmax 0.0219%, nfe) (gnomAD).

DNAJC5 p.Pro51=

c.153G>T · rs151265913 · VCV205367

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0219%, nfe)

Conditions

neuronal ceroid lipofuscinosis

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 -4.9	GERP -4.1
Overall
CADD	0.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0219% European (non-Finnish) · 258/1,180,018 alleles

Filtering AF 0.0196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.0168% 271/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0219%	4,574
Remaining individualsnot grpmax-eligible	0.0128%	7,811
Admixed American	0.00667%	14,998
African / African-American	0.00133%	74,916

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: DNAJC5
Protein: p.Pro51=
Coding: c.153G>T
MANE Select: NM_025219
dbSNP: rs151265913
Type: single nucleotide variant
Location: chr20:63929357 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 51: the j domain; an α-helix

Full DNAJC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ceroid lipofuscinosis, neuronal, 4 (Kufs type)

Similar variants

DNAJC5 p.Leu115Arg Pathogenic ★★ same condition
DNAJC5 c.-109A>G Uncertain significance ★★ same condition
DNAJC5 c.-11-2A>G Uncertain significance ★★ same condition
DNAJC5 p.Ala176Val Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Ala26Thr Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Ala54Thr Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Ala54Val Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Ala63Thr Uncertain significance ★★ ⚠ 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/dnajc5-p-pro51 (accessed [today's date]).

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