ISCA1 p.Val111=
c.333G>A · rs1825290592 · VCV1555705
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
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 0.35 | GERP -1.6, phastCons 0.97 |
| Overall | ||
| CADD | 6.436 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/59,874 alleles
Filtering AF
0.00901%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00683%
Overall
0.000682%
11/1,612,746 alleles · ultra-rare
exomes 10/1,460,566 · genomes 1/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 5,987 |
| East Asian | 0.00223% | 44,896 |
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.Val111=
- Coding
- c.333G>A
- MANE Select
- NM_030940
- dbSNP
- rs1825290592
- Type
- single nucleotide variant
- Location
- chr9:86266100 (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.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
- ISCA1 p.Asn113Ser 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-val111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown