SIAE p.Thr484=
c.1452G>A · rs7941327 · VCV1168498
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 39.9%, afr) — too common for a highly-penetrant pathogenic allele
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 -14 | GERP -3.9 |
| Overall | ||
| CADD | 0.119 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
39.9%
African / African-American · 29,879/74,848 alleles
Filtering AF
39.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 39.4%
Overall
4.6%
74,305/1,613,918 alleles · common
exomes 54,455/1,461,890 · genomes 19,850/152,028 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 39.9% | 3 |
| East Asian | 13.2% | 8 |
| Remaining individualsnot grpmax-eligible | 6.07% | 16 |
| Admixed American | 4.54% | 22 |
| Ashkenazi Jewishnot grpmax-eligible | 3.99% | 25 |
| South Asian | 3.49% | 29 |
| Middle Eastern | 3.28% | 30 |
| European (non-Finnish) | 2.29% | 44 |
| Finnishnot grpmax-eligible | 0.636% | 157 |
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.Thr484=
- Coding
- c.1452G>A
- MANE Select
- NM_170601
- dbSNP
- rs7941327
- Type
- single nucleotide variant
- Location
- chr11:124637071 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.26
Similar variants
- SIAE p.Thr484Met Uncertain significance ★ ⚠ same residue
- 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
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-thr484 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown