EARS2 p.His243=
c.729C>T · rs577733714 · VCV1663857
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0209%, 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 -4.1 | GERP -2.8 |
| Overall | ||
| CADD | 4.566 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0209%
South Asian · 19/90,778 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.0018%
29/1,611,918 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0209% | 4,778 |
| African / African-American | 0.00267% | 37,501 |
| East Asian | 0.00223% | 44,848 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,360 |
| European (non-Finnish) | 0.000509% | 196,555 |
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
- EARS2
- Protein
- p.His243=
- Coding
- c.729C>T
- MANE Select
- NM_001083614
- dbSNP
- rs577733714
- Type
- single nucleotide variant
- Location
- chr16:23535117 (GRCh38)
- Gene constraint
- LOEUF 1.138 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.84
Similar variants
- EARS2 p.His243Arg Uncertain significance ★ ⚠ same residue
- EARS2 p.Arg107His Pathogenic/Likely pathogenic ★★ ⚠ same type
- EARS2 p.Arg108Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- EARS2 p.Cys167Tyr Pathogenic/Likely pathogenic ★★ same type
- EARS2 p.Gly317Cys Pathogenic ★★ same type
- EARS2 p.Met1Val Pathogenic/Likely pathogenic ★★ same type
- EARS2 p.Ser143Ter Pathogenic ★★ same type
- EARS2 p.Ala263Thr 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/ears2-p-his243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown