KARS1 p.Pro409=
c.1227A>G · VCV3728813
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -1.6 | GERP -2.9 |
| Overall | ||
| CADD | 6.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.000124%
2/1,614,222 alleles · ultra-rare
exomes 2/1,461,858 · genomes 0/152,364 · joint denominator
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
- KARS1
- Protein
- p.Pro409=
- Coding
- c.1227A>G
- MANE Select
- NM_005548
- Type
- single nucleotide variant
- Location
- chr16:75631441 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.23 · 14 PDB
- Residue 409
- an α-helix
Similar variants
- KARS1 p.Pro409Ala Uncertain significance ★ ⚠ same residue
- KARS1 p.Arg230Ser Likely pathogenic ★★ same type
- KARS1 p.Asn563Ile Pathogenic/Likely pathogenic ★★ same type
- KARS1 p.Pro200Leu Pathogenic/Likely pathogenic ★★ same type
- KARS1 p.Pro505Arg Likely pathogenic ★★ same type
- KARS1 p.Thr559Met Pathogenic/Likely pathogenic ★★ same type
- KARS1 c.63-2623G>A Uncertain significance ★★ same type
- KARS1 c.63-2657A>T 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/kars1-p-pro409 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown