EARS2 p.Arg108=
c.324G>A · rs776813068 · VCV2955579
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, 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 -1.8 | GERP -3.7 |
| Overall | ||
| CADD | 7.882 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
South Asian · 16/89,998 alleles
Filtering AF
0.0111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00908%
Overall
0.00193%
31/1,606,760 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0178% | 5,625 |
| Admixed American | 0.0119% | 8,402 |
| Remaining individualsnot grpmax-eligible | 0.00483% | 20,718 |
| European (non-Finnish) | 0.000425% | 235,542 |
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.Arg108=
- Coding
- c.324G>A
- MANE Select
- NM_001083614
- dbSNP
- rs776813068
- Type
- single nucleotide variant
- Location
- chr16:23544675 (GRCh38)
- Gene constraint
- LOEUF 1.138 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.84
- Residue 108
- a UniProt-annotated variant site (in coxpd12)
Similar variants
- EARS2 p.Arg108Trp Pathogenic/Likely pathogenic ★★ ⚠ same residue
- EARS2 p.Arg107His 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-arg108 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown