ASIC4 p.Pro113=
c.339G>A · rs35780339 · VCV714981
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.29%, 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 -4.8 | GERP -3.5 |
| Overall | ||
| CADD | 8.104 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.29%
African / African-American · 1,720/75,038 alleles
Filtering AF
2.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.17%
Overall
0.123%
1,981/1,613,460 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.29% | 44 |
| Remaining individualsnot grpmax-eligible | 0.166% | 601 |
| Admixed American | 0.125% | 800 |
| East Asian | 0.0892% | 1,121 |
| Middle Eastern | 0.0495% | 2,021 |
| South Asian | 0.00329% | 30,361 |
| European (non-Finnish) | 0.00305% | 32,777 |
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
- ASIC4
- Protein
- p.Pro113=
- Coding
- c.339G>A
- MANE Select
- NM_018674
- dbSNP
- rs35780339
- Type
- single nucleotide variant
- Location
- chr2:219515063 (GRCh38)
- Gene constraint
- LOEUF 0.69 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.37
Similar variants
- ASIC4 p.Ala127= Benign ★★ same type
- ASIC4 p.Ala298Thr Benign ★★ same type
- ASIC4 p.Arg475= Benign ★★ same type
- ASIC4 p.Val33Ala Likely benign ★★ same type
- ASIC4 p.Glu383Lys Uncertain significance ★ same type
- ASIC4 p.Pro368= Likely benign ★ same type
- ASIC4 p.Thr245= Likely benign ★ 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/asic4-p-pro113 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown