DNAJC13 p.Ser421=
c.1263A>C · VCV4684718
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.047%, nfe)
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 -0.81 | GERP -3.5 |
| Overall | ||
| CADD | 6.814 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.047%
European (non-Finnish) · 554/1,179,972 alleles
Filtering AF
0.0436%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0424%
Overall
0.0354%
571/1,613,988 alleles · ultra-rare
exomes 536/1,461,796 · genomes 35/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.047% | 2,130 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,927 |
| Finnishnot grpmax-eligible | 0.00625% | 16,010 |
| African / African-American | 0.00534% | 18,731 |
| Admixed American | 0.00333% | 30,000 |
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
- DNAJC13
- Protein
- p.Ser421=
- Coding
- c.1263A>C
- MANE Select
- NM_015268
- Type
- single nucleotide variant
- Location
- chr3:132456746 (GRCh38)
- Gene constraint
- LOEUF 0.267 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 82.91
- Residue 421
- the 'involved in membrane association' region
Similar variants
- DNAJC13 p.Arg677Trp Uncertain significance ★★ ⚠ same type
- DNAJC13 p.Arg833Lys Uncertain significance ★★ ⚠ same type
- DNAJC13 p.Ile2055Leu Uncertain significance ★★ ⚠ same type
- DNAJC13 p.Leu1834Val Uncertain significance ★★ ⚠ same type
- DNAJC13 p.Met688Val Uncertain significance ★★ ⚠ same type
- DNAJC13 p.Thr66Met Uncertain significance ★★ ⚠ same type
- DNAJC13 c.1349+102C>T Benign ★★ same type
- DNAJC13 c.1349+103C>A 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/dnajc13-p-ser421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown