LARS2 p.Pro377=
c.1131C>T · rs144183054 · VCV226692
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 7.63%, amr) — 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 -0.07 | GERP -1.3, phastCons 0.6 |
| Overall | ||
| CADD | 9.142 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.63%
Admixed American · 4,577/60,006 alleles
Filtering AF
7.44%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.37%
Overall
0.31%
4,972/1,601,306 alleles · common
exomes 4,160/1,449,010 · genomes 812/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 7.63% | 13 |
| Remaining individualsnot grpmax-eligible | 0.348% | 288 |
| African / African-American | 0.0923% | 1,083 |
| East Asian | 0.0759% | 1,318 |
| South Asian | 0.0286% | 3,494 |
| European (non-Finnish) | 0.00428% | 23,366 |
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.Pro377=
- Coding
- c.1131C>T
- MANE Select
- NM_015340
- dbSNP
- rs144183054
- Type
- single nucleotide variant
- Location
- chr3:45488704 (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-pro377 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown