EARS2 p.Ala429=
c.1287A>T · rs374785094 · VCV2179920
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00644%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.67 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.40 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -8.9 | GERP -3.7 |
| Overall | ||
| CADD | 11.22 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00644%
European (non-Finnish) · 76/1,180,032 alleles
Filtering AF
0.00527%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.00477%
77/1,614,042 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00644% | 15,527 |
| South Asian | 0.0011% | 91,072 |
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.Ala429=
- Coding
- c.1287A>T
- MANE Select
- NM_001083614
- dbSNP
- rs374785094
- Type
- single nucleotide variant
- Location
- chr16:23529567 (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.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-ala429 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown