Is DNAJC5 p.Lys56= (c.168G>A) pathogenic?

DNAJC5 p.Lys56= (c.168G>A) is classified Likely benign in DNAJC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-20). Very rare (popmax 8.47e-05%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Lys56= (c.168G>A)?

DNAJC5 p.Lys56= (c.168G>A) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Lys56= (c.168G>A) in the general population?

DNAJC5 p.Lys56= (c.168G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

DNAJC5 p.Lys56=

c.168G>A · rs1438841329 · VCV1996827

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 2.2	GERP -1.4, phastCons 1
Overall
CADD	8.628	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,848 alleles · very rare

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.Lys56=
Coding: c.168G>A
MANE Select: NM_025219
dbSNP: rs1438841329
Type: single nucleotide variant
Location: chr20:63929372 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 56: the j domain; an α-helix; a modified residue (n6-acetyllysine)

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

Similar variants

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
DNAJC5 p.Arg164Lys Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Arg36Gln Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Arg36Pro 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-lys56 (accessed [today's date]).

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