CES1 p.Ala45=
c.135A>G · VCV4930016
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.81%, sas)
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 -6.7 | GERP -3.6 |
| Overall | ||
| CADD | 5.255 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.81%
South Asian · 2,551/90,694 alleles
Filtering AF
2.72%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.68%
Overall
0.177%
2,853/1,613,810 alleles · low-frequency
exomes 2,689/1,461,434 · genomes 164/152,376 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.81% | 36 |
| Remaining individualsnot grpmax-eligible | 0.347% | 288 |
| Middle Eastern | 0.0825% | 1,212 |
| East Asian | 0.0535% | 1,870 |
| Admixed American | 0.04% | 2,501 |
| African / African-American | 0.00799% | 12,513 |
| European (non-Finnish) | 0.0022% | 45,386 |
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
- CES1
- Protein
- p.Ala45=
- Coding
- c.135A>G
- MANE Select
- NM_001025195
- Type
- single nucleotide variant
- Location
- chr16:55828892 (GRCh38)
- Gene constraint
- LOEUF 1.272 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.27 · 21 PDB
Similar variants
- CES1 p.Ala45Val Uncertain significance ★ ⚠ same residue
- CES1 p.Val166Met Uncertain significance ★★ ⚠ same type
- CES2 p.Glu366= Benign ★★ same type
- CES1 p.Ala126Asp Uncertain significance ★ ⚠ same type
- CES1 p.Ala126Val Uncertain significance ★ ⚠ same type
- CES1 p.Ala149Glu Uncertain significance ★ ⚠ same type
- CES1 p.Ala160Thr Uncertain significance ★ ⚠ same type
- CES1 p.Ala197Asp 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/ces1-p-ala45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown