Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.49%, afr)
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 -9.3 | GERP -4 |
| Overall | ||
| CADD | 0.175 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.49%
African / African-American · 3,369/75,034 alleles
Filtering AF
4.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.31%
Overall
0.25%
4,033/1,613,134 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.49% | 22 |
| Admixed American | 0.545% | 184 |
| Remaining individualsnot grpmax-eligible | 0.354% | 283 |
| Middle Eastern | 0.297% | 337 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0811% | 1,234 |
| South Asian | 0.0154% | 6,506 |
| European (non-Finnish) | 0.00483% | 20,702 |
| East Asian | 0.00446% | 22,437 |
| Finnishnot grpmax-eligible | 0.00159% | 63,010 |
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
- AMBRA1
- Protein
- p.Ser492=
- Coding
- c.1476G>A
- MANE Select
- NM_001387011
- dbSNP
- rs2864836
- Type
- single nucleotide variant
- Location
- chr11:46542541 (GRCh38)
- Gene constraint
- LOEUF 0.491 · pLI 0.94 (gnomAD)
- Structure
- AlphaFold pLDDT 49.27 · 2 PDB
- Residue 492
- the 'disordered' region
Similar variants
- AMBRA1 p.Ala927= Benign ★★ same type
- AMBRA1 p.Ser434= Benign ★★ same type
- AMBRA1 p.Ala1142Val Uncertain significance ★ ⚠ same type
- AMBRA1 p.Ala1147Gly Uncertain significance ★ ⚠ same type
- AMBRA1 p.Ala1147Val Uncertain significance ★ ⚠ same type
- AMBRA1 p.Ala1288Thr Uncertain significance ★ ⚠ same type
- AMBRA1 p.Ala355Thr Uncertain significance ★ ⚠ same type
- AMBRA1 p.Ala984Val 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/ambra1-p-ser492 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown