DOLK p.Pro8=
c.24G>A · rs746403097 · VCV1079180
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
2
Cardiovascular phenotype
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 -0.14 | GERP -3.8, phastCons 0.001 |
| Overall | ||
| CADD | 4.506 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,868 alleles
Overall
0.000248%
4/1,612,880 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,868 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,412 |
| African / African-American | 0.00134% | 74,892 |
| South Asian | 0.0011% | 91,048 |
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
- DOLK
- Protein
- p.Pro8=
- Coding
- c.24G>A
- MANE Select
- NM_014908
- dbSNP
- rs746403097
- Type
- single nucleotide variant
- Location
- chr9:128947280 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.37
Similar variants
- DOLK p.Pro8Ser Uncertain significance ★★ ⚠ same residue
- DOLK p.Pro8Ala Uncertain significance ★ ⚠ same residue
- DOLK p.His408Asp Pathogenic/Likely pathogenic ★★ same condition
- DOLK p.Met1Ile Pathogenic/Likely pathogenic ★★ same condition
- DOLK p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
- DOLK c.-194G>T Uncertain significance ★★ same condition
- DOLK c.-22G>A Uncertain significance ★★ same condition
- DOLK c.-269G>T Uncertain significance ★★ same condition
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/dolk-p-pro8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown