Is DNAJC5 p.Val19Ile (c.55G>A) pathogenic?

DNAJC5 p.Val19Ile (c.55G>A) is classified Uncertain significance in DNAJC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-05). AlphaMissense: likely benign (0.0899); Very rare (popmax 0.0022%, sas); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Val19Ile (c.55G>A)?

DNAJC5 p.Val19Ile (c.55G>A) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Val19Ile (c.55G>A) in the general population?

DNAJC5 p.Val19Ile (c.55G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about DNAJC5 p.Val19Ile (c.55G>A)?

AlphaMissense predicts likely benign (score 0.0899) — an in-silico prediction, not a clinical call.

DNAJC5 p.Val19Ile

c.55G>A · rs981499477 · VCV1419185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0899 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.0899	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -7.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 1,095 bp · p 0.0039 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000496% 8/1,613,880 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,542
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000339%	295,005

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.Val19Ile
Coding: c.55G>A
MANE Select: NM_025219
dbSNP: rs981499477
Type: single nucleotide variant
Location: chr20:63928400 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 19: 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.Val19= 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.Ala63Thr 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-val19ile (accessed [today's date]).

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