EARS2 p.Lys287=
c.861G>A · rs200580645 · VCV734938
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.151%, 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 1.8 | GERP 0.72, phastCons 1 |
| Overall | ||
| CADD | 10.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.151%
African / African-American · 113/75,028 alleles
Filtering AF
0.128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.12%
Overall
0.00843%
136/1,612,832 alleles · rare
exomes 71/1,460,522 · genomes 65/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.151% | 664 |
| Middle Eastern | 0.0704% | 1,420 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,244 |
| Admixed American | 0.01% | 9,993 |
| South Asian | 0.0011% | 90,918 |
| European (non-Finnish) | 0.00017% | 589,723 |
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.Lys287=
- Coding
- c.861G>A
- MANE Select
- NM_001083614
- dbSNP
- rs200580645
- Type
- single nucleotide variant
- Location
- chr16:23534985 (GRCh38)
- Gene constraint
- LOEUF 1.138 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.84
- Residue 287
- a binding site
Similar variants
- 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
- EARS2 p.Ala299Val 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-lys287 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown