Is DNAJC5 p.Lys41Arg (c.122A>G) pathogenic?

DNAJC5 p.Lys41Arg (c.122A>G) is classified Conflicting classifications of pathogenicity in DNAJC5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-06-10). AlphaMissense: likely benign (0.1315); Very rare (popmax 0.000763%, nfe); Associated with ceroid lipofuscinosis, neuronal, 4 (Kufs type).

What condition is associated with DNAJC5 p.Lys41Arg (c.122A>G)?

DNAJC5 p.Lys41Arg (c.122A>G) is associated with ceroid lipofuscinosis, neuronal, 4 (Kufs type), neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Lys41Arg (c.122A>G) in the general population?

DNAJC5 p.Lys41Arg (c.122A>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about DNAJC5 p.Lys41Arg (c.122A>G)?

AlphaMissense predicts likely benign (score 0.1315) — an in-silico prediction, not a clinical call.

DNAJC5 p.Lys41Arg

c.122A>G · rs528096976 · VCV339356

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1315 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ceroid lipofuscinosis, neuronal, 4 (Kufs type)

Computational evidence

Protein change
AlphaMissense	0.1315	likely benign
REVEL	0.342	indeterminate
SaProt	LLR -8.21	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 1,095 bp · p 0.0039 · regional, not allelic
Overall
CADD	22.6	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 0.000763% European (non-Finnish) · 9/1,179,968 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,678 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.Lys41Arg
Coding: c.122A>G
MANE Select: NM_025219
dbSNP: rs528096976
Type: single nucleotide variant
Location: chr20:63929326 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 41: the j domain; an α-helix

Full DNAJC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ceroid lipofuscinosis, neuronal, 4 (Kufs type) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronal ceroid lipofuscinosis

For CLN4 disease (Orphanet):

Onset: Adult

Similar variants

DNAJC5 p.Leu115Arg Pathogenic ★★ same condition
DNAJC5 c.-109A>G Uncertain significance ★★ same condition
DNAJC5 c.-11-2A>G Uncertain significance ★★ same condition
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

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-lys41arg (accessed [today's date]).

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