Is DNAJC5 p.Arg36Pro (c.107G>C) pathogenic?

DNAJC5 p.Arg36Pro (c.107G>C) is classified Uncertain significance in DNAJC5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-13). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Arg36Pro (c.107G>C)?

DNAJC5 p.Arg36Pro (c.107G>C) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Arg36Pro (c.107G>C) in the general population?

DNAJC5 p.Arg36Pro (c.107G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC5 p.Arg36Pro (c.107G>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

DNAJC5 p.Arg36Pro

c.107G>C · VCV3664128

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 5% in DNAJC5
REVEL	0.837	moderately pathogenic-leaning
SaProt	LLR -14.90	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 9.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 1,095 bp · p 0.0039 · regional, not allelic
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAJC5
Protein: p.Arg36Pro
Coding: c.107G>C
MANE Select: NM_025219
Type: single nucleotide variant
Location: chr20:63928452 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 36: 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.Arg36Gln Uncertain significance ★★ ⚠ same residue
DNAJC5 p.Arg36= Uncertain significance ★ same residue
DNAJC5 p.Arg36Trp Uncertain significance ★ ⚠ 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

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-arg36pro (accessed [today's date]).

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