DZIP1L p.Ser758=
c.2274C>T · rs890924178 · VCV2081162
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, 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 0.7 | GERP -0.77, phastCons 0.12 |
| Overall | ||
| CADD | 0.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,030 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.00031%
5/1,614,140 alleles · very rare
exomes 5/1,461,798 · genomes 0/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,015 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| European (non-Finnish) | 8.47e-05% | 1,180,052 |
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.Ser758=
- Coding
- c.2274C>T
- MANE Select
- NM_173543
- dbSNP
- rs890924178
- Type
- single nucleotide variant
- Location
- chr3:138062846 (GRCh38)
- Gene constraint
- LOEUF 1.257 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.03
- Residue 758
- a UniProt-annotated variant site (in pkd5); the 'disordered' region
Similar variants
- DZIP1L p.Ser758Asn Uncertain significance ★★ ⚠ same residue
- 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
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-ser758 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown