DOLK p.Ala504=
c.1512T>C · rs183735415 · VCV705536
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.095%, amr)
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 0.075 | GERP -2.8, phastCons 0.07 |
| Overall | ||
| CADD | 2.859 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.095%
Admixed American · 57/60,020 alleles
Filtering AF
0.0752%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0681%
Overall
0.00353%
57/1,614,198 alleles · ultra-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.Ala504=
- Coding
- c.1512T>C
- MANE Select
- NM_014908
- dbSNP
- rs183735415
- Type
- single nucleotide variant
- Location
- chr9:128945792 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.37
- Residue 504
- a UniProt-annotated variant site (in cdg1m)
Similar variants
- DOLK p.Ala504Thr Uncertain significance ★★ ⚠ same residue
- DOLK p.Ala504Ser 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-ala504 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown