DOLK p.Leu489=
c.1467G>T · rs955285603 · VCV390557
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00229%, nfe)
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 0.048 | GERP -3.3, phastCons 0.85 |
| Overall | ||
| CADD | 1.641 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00229%
European (non-Finnish) · 27/1,180,056 alleles
Filtering AF
0.00157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00134%
Overall
0.00167%
27/1,614,106 alleles · very rare
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.Leu489=
- Coding
- c.1467G>T
- MANE Select
- NM_014908
- dbSNP
- rs955285603
- Type
- single nucleotide variant
- Location
- chr9:128945837 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.37
- Residue 489
- a UniProt-annotated variant site (in cdg1m)
Similar variants
- 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
- DOLK p.Ala115Val Uncertain significance ★★ ⚠ same condition
- DOLK p.Ala129Ser 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-leu489 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown