SKIC3 p.Ala1237=
c.3711G>A · rs147416417 · VCV1470759
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, afr)
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 0.063 | GERP -2.2, phastCons 0.31 |
| Overall | ||
| CADD | 8.377 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/74,952 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00904%
Overall
0.00304%
49/1,613,526 alleles · ultra-rare
exomes 35/1,461,460 · genomes 14/152,066 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,354 |
| East Asian | 0.0067% | 14,933 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| European (non-Finnish) | 0.00237% | 42,136 |
| South Asian | 0.0022% | 45,529 |
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
- SKIC3
- Protein
- p.Ala1237=
- Coding
- c.3711G>A
- MANE Select
- NM_014639
- dbSNP
- rs147416417
- Type
- single nucleotide variant
- Location
- chr5:95494773 (GRCh38)
- Structure
- AlphaFold pLDDT 86.17 · 7 PDB
- Residue 1237
- an α-helix
Similar variants
- SKIC3 p.Ala1237Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- SKIC3 c.1221+1G>C Likely pathogenic ★★ same type
- SKIC3 c.1633-2A>G Pathogenic/Likely pathogenic ★★ same type
- SKIC3 c.1757+1G>A Likely pathogenic ★★ same type
- SKIC3 c.2921-1G>A Pathogenic/Likely pathogenic ★★ same type
- SKIC3 c.2921-2A>G Pathogenic ★★ same type
- SKIC3 p.Arg1209Ter Pathogenic/Likely pathogenic ★★ same type
- SKIC3 p.Arg137Ter Pathogenic/Likely pathogenic ★★ 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/skic3-p-ala1237 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown