LARS2 p.Ser575=
c.1725T>C · VCV4962030
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00968%, sas)
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 -0.059 | GERP -3.1, phastCons 0.84 |
| Overall | ||
| CADD | 7.008 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00968%
South Asian · 8/82,636 alleles
Filtering AF
0.00475%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0035%
Overall
0.000573%
9/1,569,316 alleles · very rare
exomes 8/1,417,078 · genomes 1/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00968% | 10,330 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,778 |
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
- LARS2
- Protein
- p.Ser575=
- Coding
- c.1725T>C
- MANE Select
- NM_015340
- Type
- single nucleotide variant
- Location
- chr3:45500544 (GRCh38)
- Gene constraint
- LOEUF 0.808 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.57
Similar variants
- LARS2 c.235-2A>G Likely pathogenic ★★ same type
- LARS2 p.Arg228His Likely pathogenic ★★ same type
- LARS2 p.Arg663Trp Pathogenic/Likely pathogenic ★★ same type
- LARS2 p.Arg66Ter Pathogenic/Likely pathogenic ★★ same type
- LARS2 p.Asn153His Pathogenic/Likely pathogenic ★★ same type
- LARS2 p.Asp438Gly Likely pathogenic ★★ ⚠ same type
- LARS2 p.Gln147Pro Likely pathogenic ★★ ⚠ same type
- LARS2 p.Gln186Ter 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/lars2-p-ser575 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown