Is DNAJC5 p.Ala63Val (c.188C>T) pathogenic?

DNAJC5 p.Ala63Val (c.188C>T) is classified Conflicting classifications of pathogenicity in DNAJC5 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-05-30). AlphaMissense: likely pathogenic (0.9972); Ultra-rare (popmax 0.0164%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Ala63Val (c.188C>T)?

DNAJC5 p.Ala63Val (c.188C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Ala63Val (c.188C>T) in the general population?

DNAJC5 p.Ala63Val (c.188C>T) is ultra-rare (popmax 0.0164%, nfe) (gnomAD).

What do computational predictors say about DNAJC5 p.Ala63Val (c.188C>T)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

DNAJC5 p.Ala63Val

c.188C>T · rs139312819 · VCV558992

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic
REVEL	0.776	moderately pathogenic-leaning
SaProt	LLR -12.01	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 1,095 bp · p 0.0039 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.0164% European (non-Finnish) · 193/1,180,044 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.0129% 209/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0164%	6,114
African / African-American	0.0147%	6,811
Remaining individualsnot grpmax-eligible	0.0048%	20,827
East Asian	0.00223%	44,874
Admixed American	0.00167%	60,012

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.Ala63Val
Coding: c.188C>T
MANE Select: NM_025219
dbSNP: rs139312819
Type: single nucleotide variant
Location: chr20:63929392 (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.Ala63= Likely benign ★★ 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-ala63val (accessed [today's date]).

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