Is DNAJC5 p.Ala63= (c.189G>A) pathogenic?

DNAJC5 p.Ala63= (c.189G>A) is classified Likely benign in DNAJC5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-07-01). Ultra-rare (popmax 0.0657%, mid); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Ala63= (c.189G>A)?

DNAJC5 p.Ala63= (c.189G>A) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Ala63= (c.189G>A) in the general population?

DNAJC5 p.Ala63= (c.189G>A) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

DNAJC5 p.Ala63=

c.189G>A · rs746052000 · VCV390170

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, 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 -3.5	GERP -4.3
Overall
CADD	9.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00403% 65/1,614,000 alleles · ultra-rare exomes 63/1,461,842 · genomes 2/152,158 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00441%	22,693
South Asian	0.0022%	45,539
Admixed American	0.00167%	60,000
African / African-American	0.00133%	74,920

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.Ala63=
Coding: c.189G>A
MANE Select: NM_025219
dbSNP: rs746052000
Type: single nucleotide variant
Location: chr20:63929393 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 63: 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

Similar variants

DNAJC5 p.Ala63Thr Uncertain significance ★★ ⚠ same residue
DNAJC5 p.Ala63Val Conflicting classifications of pathogenicity ★ ⚠ same residue
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.Arg164Lys Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Arg36Gln 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-ala63 (accessed [today's date]).

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