SIAE p.Ala3=
c.9G>A · rs770643480 · VCV2962788
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0494%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.7 | GERP -4.2 |
| Overall | ||
| CADD | 4.023 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0494%
Middle Eastern · 3/6,078 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00716%
Overall
0.000806%
13/1,613,408 alleles · ultra-rare
exomes 10/1,461,310 · genomes 3/152,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0494% | 2,026 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,380 |
| European (non-Finnish) | 0.000763% | 131,086 |
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.Ala3=
- Coding
- c.9G>A
- MANE Select
- NM_170601
- dbSNP
- rs770643480
- Type
- single nucleotide variant
- Location
- chr11:124673700 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.26
- Residue 3
- a UniProt-annotated variant site (rare variant found in a patient with crohn disease; probably not involved in disease susceptibility; the mutant enzyme has normal activity and is normally secreted)
Similar variants
- SPA17 p.Ile3Val Uncertain significance ★★ ⚠ same residue
- SIAE p.Ala3Gly Likely benign ★★ same residue
- SIAE p.Ala3Val 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
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-ala3 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown