ASIC2 p.Leu69Val
c.205C>G · VCV3436325
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00998%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.101 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP -0.34, phastCons 1 |
| Regional constraint | o/e 0.96 | unconstrained · MANE · 180 kb · p 0.42 · regional, not allelic |
| Overall | ||
| CADD | 19.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00998%
South Asian · 9/90,200 alleles
Filtering AF
0.00518%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00389%
Overall
0.000762%
11/1,442,826 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00998% | 10,022 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 30,996 |
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
- ASIC2
- Protein
- p.Leu69Val
- Coding
- c.205C>G
- MANE Select
- NM_183377
- Type
- single nucleotide variant
- Location
- chr17:33291911 (GRCh38)
- Gene constraint
- LOEUF 0.591 · pLI 0.20 (gnomAD)
- Structure
- AlphaFold pLDDT 86.90 · 1 PDB
Similar variants
- ASIC2 c.988-4G>A Benign ★★ same type
- ASIC2 p.Ala293= Benign ★★ same type
- ASIC2 p.Ala129Thr Uncertain significance ★ ⚠ same type
- ASIC2 p.Ala136Val Uncertain significance ★ ⚠ same type
- ASIC2 p.Ala28Glu Uncertain significance ★ same type
- ASIC2 p.Ala382Val Uncertain significance ★ ⚠ same type
- ASIC2 p.Ala402Val Uncertain significance ★ ⚠ same type
- ASIC2 p.Ala47Thr 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/asic2-p-leu69val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown