DHX9 p.Lys593=
c.1779G>A · VCV3771571
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, 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 3 | GERP -2.1, phastCons 1 |
| Overall | ||
| CADD | 10.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,012 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000479%
7/1,461,096 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,012 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
| European (non-Finnish) | 0.000424% | 235,889 |
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
- DHX9
- Protein
- p.Lys593=
- Coding
- c.1779G>A
- MANE Select
- NM_001357
- Type
- single nucleotide variant
- Location
- chr1:182874918 (GRCh38)
- Gene constraint
- LOEUF 0.263 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 81.84 · 7 PDB
- Residue 593
- the 'necessary for interaction with rna polymerase ii holoenzyme' region; the 'necessary for interaction with h2ax' region; the 'core helicase' region; the 'disordered' region; a UniProt-annotated variant site (in mrd75; likely pathogenic)
Similar variants
- DHX9 p.Ala355Thr Uncertain significance ★★ ⚠ same type
- DHX9 p.Asn1133His Uncertain significance ★★ ⚠ same type
- DHX9 p.Pro586Ala Uncertain significance ★★ ⚠ same type
- DHX9 c.364+6G>T Benign ★★ same type
- DHX9 p.Ile903= Benign ★★ same type
- DHX9 p.Leu244= Benign ★★ same type
- DHX9 p.Tyr875= Benign ★★ same type
- DHX9 c.1141-1G>A Likely pathogenic ★ 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/dhx9-p-lys593 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown