ACACA p.Thr1309=
c.3927G>A · VCV3608157
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0374%, 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 -9.6 | GERP -3.6 |
| Overall | ||
| CADD | 0.115 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0374%
South Asian · 34/91,024 alleles
Filtering AF
0.0274%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.024%
Overall
0.00645%
104/1,612,386 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0374% | 2,677 |
| Middle Eastern | 0.0165% | 6,058 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,488 |
| European (non-Finnish) | 0.00492% | 20,319 |
| East Asian | 0.00446% | 22,438 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,598 |
| Admixed American | 0.00333% | 30,006 |
| African / African-American | 0.00133% | 74,972 |
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
- ACACA
- Protein
- p.Thr1309=
- Coding
- c.3927G>A
- MANE Select
- NM_198834
- Type
- single nucleotide variant
- Location
- chr17:37206804 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.05 · 10 PDB
- Residue 1309
- an α-helix
Similar variants
- ACACA p.Thr1309Met Uncertain significance ★ ⚠ same residue
- ACACA p.Ala2308Val Uncertain significance ★★ ⚠ same type
- ACACA p.Arg1206His Uncertain significance ★★ ⚠ same type
- ACACA p.Arg2198Gln Uncertain significance ★★ ⚠ same type
- ACACA p.Arg745Trp Uncertain significance ★★ ⚠ same type
- ACACA p.Asn1903Ser Uncertain significance ★★ ⚠ same type
- ACACA p.Asn728Ser Uncertain significance ★★ ⚠ same type
- ACACA p.Asn950Ser 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/acaca-p-thr1309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown