Is DNAJC5 p.Phe148= (c.444C>T) pathogenic?

DNAJC5 p.Phe148= (c.444C>T) is classified Conflicting classifications of pathogenicity in DNAJC5 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-19). Ultra-rare (popmax 0.0183%, amr); Associated with ceroid lipofuscinosis, neuronal, 4 (Kufs type).

What condition is associated with DNAJC5 p.Phe148= (c.444C>T)?

DNAJC5 p.Phe148= (c.444C>T) is associated with ceroid lipofuscinosis, neuronal, 4 (Kufs type), neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Phe148= (c.444C>T) in the general population?

DNAJC5 p.Phe148= (c.444C>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

DNAJC5 p.Phe148=

c.444C>T · rs772254851 · VCV339358

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Conditions

ceroid lipofuscinosis, neuronal, 4 (Kufs type)

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 0.76	GERP -1.4, phastCons 1
Overall
CADD	9.455	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/60,010 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00304% 49/1,614,040 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,455
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00305%	32,779

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.Phe148=
Coding: c.444C>T
MANE Select: NM_025219
dbSNP: rs772254851
Type: single nucleotide variant
Location: chr20:63930973 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB

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-phe148 (accessed [today's date]).

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