HARS2 p.Ser26=
c.78G>A · rs746617974 · VCV2093623
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00119%, sas)
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 0.1 | GERP -3.8 |
| Overall | ||
| CADD | 5.422 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00119%
South Asian · 1/84,232 alleles
Filtering AF
0.000254%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000163%
Overall
0.000515%
8/1,552,352 alleles · very rare
exomes 8/1,399,984 · genomes 0/152,368 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00119% | 84,232 |
| European (non-Finnish) | 0.00061% | 163,945 |
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.Ser26=
- Coding
- c.78G>A
- MANE Select
- NM_012208
- dbSNP
- rs746617974
- Type
- single nucleotide variant
- Location
- chr5:140691726 (GRCh38)
- Gene constraint
- LOEUF 0.865 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.44
Similar variants
- HARS2 p.Ser26Ala Uncertain significance ★ ⚠ same residue
- 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
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-ser26 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown