DOLK p.Ala368=
c.1104G>A · rs765151256 · VCV1793334
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Conditions
1
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 -5.7 | GERP -3.3 |
| Overall | ||
| CADD | 0.686 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,020 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000684%
10/1,461,872 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,007 |
| East Asian | 0.00223% | 44,886 |
| African / African-American | 0.00133% | 75,036 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000339% | 295,009 |
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.Ala368=
- Coding
- c.1104G>A
- MANE Select
- NM_014908
- dbSNP
- rs765151256
- Type
- single nucleotide variant
- Location
- chr9:128946200 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.37
- Residue 368
- a UniProt-annotated variant site (in cdg1m)
Similar variants
- DOLK p.Ala368Val Uncertain significance ★ ⚠ same residue
- DOLK p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
- DOLK p.Ala194Val Uncertain significance ★★ ⚠ same condition
- DOLK p.Ala25Thr Uncertain significance ★★ ⚠ same condition
- DOLK p.Ala363Thr Uncertain significance ★★ ⚠ same condition
- DOLK p.Ala435Pro Uncertain significance ★★ ⚠ same condition
- DOLK p.Ala482Val Uncertain significance ★★ same condition
- DOLK p.Ala504Thr 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-ala368 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown