DARS2 p.Gly253=
c.759C>A · VCV3609294
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0214%, afr)
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 -2.4 | GERP -4.4 |
| Overall | ||
| CADD | 3.124 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0214%
African / African-American · 16/74,850 alleles
Filtering AF
0.0133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0109%
Overall
0.00112%
18/1,613,144 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0214% | 4,678 |
| Admixed American | 0.00167% | 59,952 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
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
- DARS2
- Protein
- p.Gly253=
- Coding
- c.759C>A
- MANE Select
- NM_018122
- Type
- single nucleotide variant
- Location
- chr1:173837035 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.91 · 1 PDB
Similar variants
- DARS2 c.228-15C>A Pathogenic/Likely pathogenic ★★ same type
- DARS2 c.228-16C>A Pathogenic/Likely pathogenic ★★ same type
- DARS2 c.397-2A>G Pathogenic/Likely pathogenic ★★ same type
- DARS2 c.492+2T>C Pathogenic ★★ same type
- DARS2 c.493-1G>C Likely pathogenic ★★ same type
- DARS2 p.Ala262Val Likely pathogenic ★★ ⚠ same type
- DARS2 p.Arg179His Pathogenic/Likely pathogenic ★★ same type
- DARS2 p.Arg188Ter Pathogenic/Likely pathogenic ★★ 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/dars2-p-gly253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown