SIAE p.Pro493=
c.1479C>T · rs780579758 · VCV2785923
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0132%, sas)
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 -0.13 | GERP -3.9 |
| Overall | ||
| CADD | 4.983 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0132%
South Asian · 12/91,080 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.000805%
13/1,614,118 alleles · ultra-rare
exomes 13/1,461,892 · genomes 0/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0132% | 7,590 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,508 |
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
- SIAE
- Protein
- p.Pro493=
- Coding
- c.1479C>T
- MANE Select
- NM_170601
- dbSNP
- rs780579758
- Type
- single nucleotide variant
- Location
- chr11:124637044 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.26
Similar variants
- SIAE p.Ala385Thr Uncertain significance ★★ ⚠ same type
- SIAE p.Arg301His Uncertain significance ★★ ⚠ same type
- SIAE p.Arg306Cys Uncertain significance ★★ ⚠ same type
- SIAE p.Cys196Phe Uncertain significance ★★ ⚠ same type
- SIAE p.Cys449Ser Uncertain significance ★★ ⚠ same type
- SIAE p.Gln309Arg Uncertain significance ★★ ⚠ same type
- SIAE p.Glu399Lys Uncertain significance ★★ ⚠ same type
- SIAE p.Glu488Asp 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/siae-p-pro493 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown