DARS1 p.Leu473=
c.1417T>C · rs76296777 · VCV380521
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 6.69%, afr) — too common for a highly-penetrant pathogenic allele
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 2.7 | GERP -2.4, phastCons 0.91 |
| Overall | ||
| CADD | 5.552 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.69%
African / African-American · 4,999/74,704 alleles
Filtering AF
6.54%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.47%
Overall
0.798%
12,839/1,608,994 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.69% | 15 |
| South Asian | 2.84% | 35 |
| Ashkenazi Jewishnot grpmax-eligible | 2.51% | 40 |
| Middle Eastern | 1.59% | 63 |
| East Asian | 1.43% | 70 |
| Remaining individualsnot grpmax-eligible | 1.18% | 85 |
| Admixed American | 0.655% | 153 |
| European (non-Finnish) | 0.219% | 457 |
| Finnishnot grpmax-eligible | 0.141% | 710 |
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.Leu473=
- Coding
- c.1417T>C
- MANE Select
- NM_001349
- dbSNP
- rs76296777
- Type
- single nucleotide variant
- Location
- chr2:135907405 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.69 · 3 PDB
- Residue 473
- a binding site; 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-leu473 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown