LARS2 p.Val336=
c.1008C>T · rs142803778 · VCV504761
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.842%, mid)
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 0.14 | GERP -1.4, phastCons 0.78 |
| Overall | ||
| CADD | 6.312 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.842%
Middle Eastern · 51/6,054 alleles
Filtering AF
0.658%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.592%
Overall
0.0545%
879/1,614,052 alleles · rare
exomes 787/1,461,772 · genomes 92/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.842% | 119 |
| South Asian | 0.202% | 495 |
| Admixed American | 0.108% | 923 |
| Remaining individualsnot grpmax-eligible | 0.0864% | 1,158 |
| European (non-Finnish) | 0.0437% | 2,287 |
| African / African-American | 0.012% | 8,337 |
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.Val336=
- Coding
- c.1008C>T
- MANE Select
- NM_015340
- dbSNP
- rs142803778
- Type
- single nucleotide variant
- Location
- chr3:45476617 (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-val336 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown