ACY1 p.Ser12=
c.36G>C · rs376811350 · VCV2018656
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, 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 -5.1 | GERP -3.5 |
| Overall | ||
| CADD | 2.111 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,078 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000205%
3/1,461,532 alleles · very rare
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
- ACY1
- Protein
- p.Ser12=
- Coding
- c.36G>C
- MANE Select
- NM_000666
- dbSNP
- rs376811350
- Type
- single nucleotide variant
- Location
- chr3:51984100 (GRCh38)
- Gene constraint
- LOEUF 0.9 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.55 · 1 PDB
- Residue 12
- an α-helix
Similar variants
- ACY1 p.Arg109Gly Uncertain significance ★★ ⚠ same type
- ACY1 p.Arg393His Benign/Likely benign ★★ same type
- ACY1 p.Ala326Gly Uncertain significance ★ ⚠ same type
- ACY1 p.Arg350His Uncertain significance ★ ⚠ same type
- ACY1 p.Cys331Arg Uncertain significance ★ ⚠ same type
- ACY1 p.Pro266Thr Uncertain significance ★ ⚠ same type
- ACY1 p.Ser406Ile Uncertain significance ★ ⚠ same type
- ACY1 c.1002-13C>G Likely benign ★ 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/acy1-p-ser12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown