Is DNAJC5 p.Asp69= (c.207C>T) pathogenic?

DNAJC5 p.Asp69= (c.207C>T) is classified Likely benign in DNAJC5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0493%, mid); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Asp69= (c.207C>T)?

DNAJC5 p.Asp69= (c.207C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Asp69= (c.207C>T) in the general population?

DNAJC5 p.Asp69= (c.207C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

DNAJC5 p.Asp69=

c.207C>T · rs760881795 · VCV391141

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

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 -0.53	GERP -4.3, phastCons 0.047
Overall
CADD	12.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00204% 33/1,614,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
South Asian	0.011%	9,109
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Admixed American	0.005%	20,004
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
East Asian	0.00223%	44,892
African / African-American	0.00133%	74,934
European (non-Finnish)	0.000847%	118,005

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.Asp69=
Coding: c.207C>T
MANE Select: NM_025219
dbSNP: rs760881795
Type: single nucleotide variant
Location: chr20:63929411 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 69: the j domain

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-asp69 (accessed [today's date]).

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