ASIC4 p.Pro368=
c.1104G>A · rs111598906 · VCV732882
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.216%, mid)
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 -7.8 | GERP -3.1 |
| Overall | ||
| CADD | 0.989 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.216%
Middle Eastern · 13/6,014 alleles
Filtering AF
0.153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.143%
Overall
0.0244%
393/1,613,882 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.216% | 463 |
| African / African-American | 0.177% | 564 |
| Remaining individualsnot grpmax-eligible | 0.0544% | 1,838 |
| Admixed American | 0.0417% | 2,400 |
| European (non-Finnish) | 0.0153% | 6,555 |
| South Asian | 0.00769% | 13,008 |
| East Asian | 0.00223% | 44,876 |
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.Pro368=
- Coding
- c.1104G>A
- MANE Select
- NM_018674
- dbSNP
- rs111598906
- Type
- single nucleotide variant
- Location
- chr2:219535199 (GRCh38)
- Gene constraint
- LOEUF 0.69 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.37
- Residue 368
- a disulfide bond
Similar variants
- ASIC4 p.Ala127= Benign ★★ same type
- ASIC4 p.Ala298Thr Benign ★★ same type
- ASIC4 p.Arg475= Benign ★★ same type
- ASIC4 p.Pro113= Benign ★★ same type
- ASIC4 p.Val33Ala Likely benign ★★ same type
- ASIC4 p.Glu383Lys Uncertain significance ★ 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-pro368 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown