HARS2 p.Val464=
c.1392G>C · rs368107818 · VCV2056090
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.016%, afr)
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 4 | GERP 0.67, phastCons 1 |
| Overall | ||
| CADD | 8.823 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.016%
African / African-American · 12/74,918 alleles
Filtering AF
0.00921%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00722%
Overall
0.00105%
17/1,613,926 alleles · ultra-rare
exomes 7/1,461,752 · genomes 10/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.016% | 6,243 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| Admixed American | 0.00167% | 59,992 |
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
- HARS2
- Protein
- p.Val464=
- Coding
- c.1392G>C
- MANE Select
- NM_012208
- dbSNP
- rs368107818
- Type
- single nucleotide variant
- Location
- chr5:140698009 (GRCh38)
- Gene constraint
- LOEUF 0.865 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.44
Similar variants
- HARS2 c.633+1G>A Likely pathogenic ★★ same type
- HARS2 p.Arg159Ter Pathogenic/Likely pathogenic ★★ same type
- HARS2 p.Tyr108Ter Pathogenic/Likely pathogenic ★★ same type
- HARS2 p.Arg129Cys Uncertain significance ★★ same type
- HARS2 p.Arg129His Uncertain significance ★★ ⚠ same type
- HARS2 p.Arg138His Uncertain significance ★★ ⚠ same type
- HARS2 p.Arg168Cys Uncertain significance ★★ ⚠ same type
- HARS2 p.Arg168His 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/hars2-p-val464 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown