DZIP1L p.Pro594=
c.1782C>T · rs374935280 · VCV2049116
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00703%, 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 4 | GERP 0.77, phastCons 0.99 |
| Overall | ||
| CADD | 12.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00703%
Admixed American · 4/56,900 alleles
Filtering AF
0.00382%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00349%
Overall
0.00416%
66/1,587,686 alleles · very rare
exomes 64/1,435,582 · genomes 2/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00703% | 14,225 |
| European (non-Finnish) | 0.00489% | 20,453 |
| South Asian | 0.00344% | 29,059 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,416 |
| African / African-American | 0.00135% | 74,198 |
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
- DZIP1L
- Protein
- p.Pro594=
- Coding
- c.1782C>T
- MANE Select
- NM_173543
- dbSNP
- rs374935280
- Type
- single nucleotide variant
- Location
- chr3:138068201 (GRCh38)
- Gene constraint
- LOEUF 1.257 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.03
- Residue 594
- a UniProt-annotated variant site (in pkd5); the 'disordered' region
Similar variants
- DZIP1L p.Glu358Ter Pathogenic/Likely pathogenic ★★ same type
- DZIP1L p.Ala190Val Uncertain significance ★★ ⚠ same type
- DZIP1L p.Arg124Cys Uncertain significance ★★ ⚠ same type
- DZIP1L p.Arg131Cys Uncertain significance ★★ ⚠ same type
- DZIP1L p.Arg233Gln Uncertain significance ★★ ⚠ same type
- DZIP1L p.Arg37His Uncertain significance ★★ ⚠ same type
- DZIP1L p.Arg48Trp Uncertain significance ★★ ⚠ same type
- DZIP1L p.Arg500Gln Uncertain significance ★★ ⚠ 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/dzip1l-p-pro594 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown