SPINK5 p.Arg482=
c.1444A>C · rs562426234 · VCV2414843
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
1
ichthyosis linearis circumflexa
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 2.7 | GERP 1.6, phastCons 0.008 |
| Overall | ||
| CADD | 10.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,060 alleles
Overall
0.000124%
2/1,613,764 alleles · ultra-rare
exomes 2/1,461,434 · genomes 0/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,472 |
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
- SPINK5
- Protein
- p.Arg482=
- Coding
- c.1444A>C
- MANE Select
- NM_006846
- dbSNP
- rs562426234
- Type
- single nucleotide variant
- Location
- chr5:148104965 (GRCh38)
- Gene constraint
- LOEUF 0.908 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.37 · 6 PDB
- Residue 482
- the kazal-like 7 domain
Similar variants
- SPINK5 c.1302+4A>T Pathogenic ★★ same condition
- SPINK5 c.1430+1G>T Pathogenic/Likely pathogenic ★★ same condition
- SPINK5 c.1431-12G>A Pathogenic/Likely pathogenic ★★ same condition
- SPINK5 c.2240+1G>A Pathogenic ★★ same condition
- SPINK5 c.2740-1G>C Likely pathogenic ★★ same condition
- SPINK5 c.666+1G>A Pathogenic/Likely pathogenic ★★ same condition
- SPINK5 c.81+2T>A Pathogenic ★★ same condition
- SPINK5 c.81+5G>A Pathogenic/Likely pathogenic ★★ same condition
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/spink5-p-arg482 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown