DARS1 p.Gln251=
c.753G>A · rs145963861 · VCV757428
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.116%, mid)
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 -0.77 | GERP -3.2, phastCons 0.007 |
| Overall | ||
| CADD | 4.801 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.116%
Middle Eastern · 7/6,016 alleles
Filtering AF
0.0545%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0387%
Overall
0.0071%
113/1,591,480 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.116% | 859 |
| Admixed American | 0.0456% | 2,193 |
| Remaining individualsnot grpmax-eligible | 0.0293% | 3,413 |
| African / African-American | 0.00542% | 18,450 |
| European (non-Finnish) | 0.00487% | 20,524 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00342% | 29,202 |
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
- DARS1
- Protein
- p.Gln251=
- Coding
- c.753G>A
- MANE Select
- NM_001349
- dbSNP
- rs145963861
- Type
- single nucleotide variant
- Location
- chr2:135922842 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.69 · 3 PDB
- Residue 251
- the 'aspartate' region; an α-helix
Similar variants
- DARS1 p.Gln251Pro Uncertain significance ★ ⚠ same residue
- DARS1 p.Ala429Thr Uncertain significance ★★ ⚠ same type
- DARS1 p.Arg197Cys Uncertain significance ★★ ⚠ same type
- DARS1 p.Arg498Gln Uncertain significance ★★ ⚠ same type
- DARS1 p.Arg63His Uncertain significance ★★ ⚠ same type
- DARS1 p.Arg81His Uncertain significance ★★ ⚠ same type
- DARS1 p.Asn233Ser Uncertain significance ★★ ⚠ same type
- DARS1 p.Glu357Lys 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/dars1-p-gln251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown