DARS1 p.Leu375=
c.1125G>A · rs769425671 · VCV1682550
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
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 -0.17 | GERP -1.4, phastCons 0.31 |
| Overall | ||
| CADD | 6.977 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,842 alleles
Filtering AF
0.00429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00296%
Overall
0.0015%
22/1,468,206 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 9,974 |
| Remaining individualsnot grpmax-eligible | 0.00347% | 28,789 |
| European (non-Finnish) | 0.00134% | 74,778 |
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.Leu375=
- Coding
- c.1125G>A
- MANE Select
- NM_001349
- dbSNP
- rs769425671
- Type
- single nucleotide variant
- Location
- chr2:135914493 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.69 · 3 PDB
- Residue 375
- an α-helix
Similar variants
- 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
- DARS1 p.Gly170Arg 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-leu375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown