Is DNAJC5 p.Pro48= (c.144C>T) pathogenic?

DNAJC5 p.Pro48= (c.144C>T) is classified Benign in DNAJC5 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Common (popmax 17.3%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with DNAJC5 p.Pro48= (c.144C>T)?

DNAJC5 p.Pro48= (c.144C>T) is associated with Inborn genetic diseases, ceroid lipofuscinosis, neuronal, 4 (Kufs type), neuronal ceroid lipofuscinosis (ClinVar).

DNAJC5 p.Pro48=

Q: How common is DNAJC5 p.Pro48= (c.144C>T) in the general population?

DNAJC5 p.Pro48= (c.144C>T) is common (popmax 17.3%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.144C>T · rs113987077 · VCV196527

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 17.3%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

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 -4.2	GERP -4.1
Overall
CADD	6.762	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.3% Admixed American · 10,383/59,920 alleles

Filtering AF 17% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.9%

Overall 0.846% 13,648/1,614,020 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	17.3%	6
East Asian	3.63%	28
Remaining individualsnot grpmax-eligible	0.814%	123
South Asian	0.338%	296
African / African-American	0.32%	313
Middle Eastern	0.181%	551
European (non-Finnish)	0.0481%	2,081
Finnishnot grpmax-eligible	0.00156%	63,980

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.Pro48=
Coding: c.144C>T
MANE Select: NM_025219
dbSNP: rs113987077
Type: single nucleotide variant
Location: chr20:63929348 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 48: the j domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ceroid lipofuscinosis, neuronal, 4 (Kufs type)neuronal ceroid lipofuscinosis

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-pro48 (accessed [today's date]).

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