LARS1 p.Pro53=
c.159A>G · VCV4780764
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00234%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.9 | GERP -4.2 |
| Overall | ||
| CADD | 2.798 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00234%
East Asian · 1/42,810 alleles
Overall
0.00019%
3/1,581,090 alleles · very rare
exomes 3/1,428,916 · genomes 0/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00234% | 42,810 |
| Remaining individualsnot grpmax-eligible | 0.00164% | 60,942 |
| European (non-Finnish) | 8.59e-05% | 1,164,714 |
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
- LARS1
- Protein
- p.Pro53=
- Coding
- c.159A>G
- MANE Select
- NM_020117
- Type
- single nucleotide variant
- Location
- chr5:146172741 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.78 · 8 PDB
- Residue 53
- an α-helix
Similar variants
- LARS1 p.Arg1105Ter Pathogenic/Likely pathogenic ★★ same type
- LARS1 p.Arg413Ter Pathogenic ★★ same type
- LARS1 p.Lys243Ter Pathogenic ★★ same type
- LARS1 p.Ala411Val Uncertain significance ★★ ⚠ same type
- LARS1 p.Arg202Cys Uncertain significance ★★ same type
- LARS1 p.Arg845Gly Uncertain significance ★★ ⚠ same type
- LARS1 p.Arg956Cys Uncertain significance ★★ ⚠ same type
- LARS1 p.Asn1104Ser 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/lars1-p-pro53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown