Is DNAJC2 p.Asp523Gly (c.1568A>G) pathogenic?

DNAJC2 p.Asp523Gly (c.1568A>G) is classified Uncertain significance in DNAJC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.2601); Ultra-rare (popmax 0.0453%, afr).

How common is DNAJC2 p.Asp523Gly (c.1568A>G) in the general population?

DNAJC2 p.Asp523Gly (c.1568A>G) is ultra-rare (popmax 0.0453%, afr) (gnomAD).

What do computational predictors say about DNAJC2 p.Asp523Gly (c.1568A>G)?

AlphaMissense predicts likely benign (score 0.2601) — an in-silico prediction, not a clinical call.

DNAJC2 p.Asp523Gly

c.1568A>G · VCV4243242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2601 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2601	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -10.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 0.59, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 7,271 bp · p 0.069 · regional, not allelic
Overall
CADD	25.6	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 0.0453% African / African-American · 34/75,032 alleles

Filtering AF 0.0333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0291%

Overall 0.00359% 58/1,613,850 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0453%	2,207
Remaining individualsnot grpmax-eligible	0.0048%	20,834
Finnishnot grpmax-eligible	0.00312%	32,003
European (non-Finnish)	0.00161%	62,096

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: DNAJC2
Protein: p.Asp523Gly
Coding: c.1568A>G
MANE Select: NM_004279 · reported on NM_014377
Type: single nucleotide variant
Location: chr7:103315832 (GRCh38)

Full DNAJC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dnajc2-p-asp523gly (accessed [today's date]).

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