DNAJC3 p.Asp459=
c.1377C>T · rs149304997 · VCV739981
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0275%, amr)
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 -9.5 | GERP -5.9 |
| Overall | ||
| CADD | 0.687 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0275%
Admixed American · 16/58,094 alleles
Filtering AF
0.0172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0143%
Overall
0.0146%
235/1,607,206 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0275% | 3,631 |
| European (non-Finnish) | 0.0171% | 5,860 |
| Remaining individualsnot grpmax-eligible | 0.0129% | 7,781 |
| African / African-American | 0.00941% | 10,626 |
| East Asian | 0.00447% | 22,366 |
| South Asian | 0.00111% | 89,742 |
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
- DNAJC3
- Protein
- p.Asp459=
- Coding
- c.1377C>T
- MANE Select
- NM_006260
- dbSNP
- rs149304997
- Type
- single nucleotide variant
- Location
- chr13:95790892 (GRCh38)
- Gene constraint
- LOEUF 0.738 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.78 · 2 PDB
- Residue 459
- the j domain; the 'disordered' region
Similar variants
- DNAJC3 p.Arg393Ter Pathogenic/Likely pathogenic ★★ same type
- DNAJC3 p.Asp69Gly Uncertain significance ★★ ⚠ same type
- DNAJC3 p.Leu231Val Uncertain significance ★★ ⚠ same type
- DNAJC3 p.Ser450Cys Uncertain significance ★★ ⚠ same type
- DNAJC3 p.Thr171Ile Uncertain significance ★★ ⚠ same type
- DNAJC3 c.848+10T>C Benign ★★ same type
- DNAJC3 p.Ala54= Benign/Likely benign ★★ same type
- DNAJC3 p.Gln99= Likely benign ★★ same type
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/dnajc3-p-asp459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown