DZIP1 p.Ser497=
c.1491G>A · VCV4920297
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00833%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor loss, 46 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.2 | GERP -5.2 |
| Overall | ||
| CADD | 2.653 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,010 alleles
Filtering AF
0.00443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00404%
Overall
0.00465%
75/1,613,478 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00833% | 12,002 |
| East Asian | 0.0067% | 14,933 |
| European (non-Finnish) | 0.00551% | 18,148 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| South Asian | 0.0011% | 91,054 |
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
- DZIP1
- Protein
- p.Ser497=
- Coding
- c.1491G>A
- MANE Select
- NM_198968
- Type
- single nucleotide variant
- Location
- chr13:95599411 (GRCh38)
- Gene constraint
- LOEUF 1.01 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.55
- Residue 497
- a UniProt-annotated variant site (in spgf47; decreased protein abundance; changed ciliary basal body organization; loss of sperm flagellum assembly); the 'mediates interaction with gdi2 and rab8a' region
Similar variants
- DZIP1 p.Ser497Leu Uncertain significance ★ ⚠ same residue
- DZIP1 p.Ser497Trp Uncertain significance ⚠ same residue
- DZIP1 p.His262Arg Uncertain significance ★★ ⚠ same type
- DZIP1 p.Met664Leu Benign ★★ same type
- DZIP1 p.Thr222= Benign ★★ same type
- DZIP1 p.Ala124Val Uncertain significance ★ ⚠ same type
- DZIP1 p.Ala211Ser Uncertain significance ★ ⚠ same type
- DZIP1 p.Ala265Gly 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/dzip1-p-ser497 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown