Is DNAJC5 p.Thr71Pro (c.211A>C) pathogenic?

DNAJC5 p.Thr71Pro (c.211A>C) is classified Uncertain significance in DNAJC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-08). AlphaMissense: likely pathogenic (0.6388); Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Thr71Pro (c.211A>C)?

DNAJC5 p.Thr71Pro (c.211A>C) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Thr71Pro (c.211A>C) in the general population?

DNAJC5 p.Thr71Pro (c.211A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC5 p.Thr71Pro (c.211A>C)?

AlphaMissense predicts likely pathogenic (score 0.6388) — an in-silico prediction, not a clinical call.

DNAJC5 p.Thr71Pro

c.211A>C · rs2146305478 · VCV1486057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6388 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.6388	likely pathogenic
REVEL	0.128	moderately benign-leaning
SaProt	LLR -12.32	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.2, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 1,095 bp · p 0.0039 · regional, not allelic
Overall
CADD	28.6	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

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.Thr71Pro
Coding: c.211A>C
MANE Select: NM_025219
dbSNP: rs2146305478
Type: single nucleotide variant
Location: chr20:63929415 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 71: 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.Thr71= 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-thr71pro (accessed [today's date]).

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