SIAE p.Phe95=
c.285C>T · rs147638217 · VCV2754674
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00508%, nfe)
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 -0.23 | GERP -4.5, phastCons 0.001 |
| Overall | ||
| CADD | 5.201 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00508%
European (non-Finnish) · 60/1,180,038 alleles
Filtering AF
0.00402%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00362%
Overall
0.00378%
61/1,614,044 alleles · very rare
exomes 59/1,461,864 · genomes 2/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00508% | 19,667 |
| African / African-American | 0.00133% | 74,914 |
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.Phe95=
- Coding
- c.285C>T
- MANE Select
- NM_170601
- dbSNP
- rs147638217
- Type
- single nucleotide variant
- Location
- chr11:124660748 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.26
Similar variants
- SIAE p.Phe95fs 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-phe95 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown