ISCA1 p.Arg16=
c.48G>A · rs1234564596 · VCV1622913
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -0.15, phastCons 1 |
| Overall | ||
| CADD | 15.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
East Asian · 9/41,440 alleles
Filtering AF
0.0113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00845%
Overall
0.0018%
28/1,554,978 alleles · ultra-rare
exomes 24/1,402,750 · genomes 4/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0217% | 4,604 |
| Middle Eastern | 0.017% | 5,880 |
| Remaining individualsnot grpmax-eligible | 0.0116% | 8,602 |
| African / African-American | 0.00136% | 73,378 |
| European (non-Finnish) | 0.00087% | 114,938 |
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
- ISCA1
- Protein
- p.Arg16=
- Coding
- c.48G>A
- MANE Select
- NM_030940
- dbSNP
- rs1234564596
- Type
- single nucleotide variant
- Location
- chr9:86282411 (GRCh38)
- Gene constraint
- LOEUF 1.785 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.18
Similar variants
- ISCA1 c.241+92G>A Benign ★★ same type
- ISCA1 p.Asn116= Benign ★★ same type
- ISCA1 p.Val111= Likely benign ★★ same type
- ISCA1 p.Ala31Thr Uncertain significance ★ ⚠ same type
- ISCA1 p.Ala8Ser Uncertain significance ★ ⚠ same type
- ISCA1 p.Arg7Pro Uncertain significance ★ ⚠ same type
- ISCA1 p.Arg83Lys Uncertain significance ★ ⚠ same type
- ISCA1 p.Arg83Ser 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/isca1-p-arg16 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown