ACAA2 c.753+19A>T
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 35.2%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +19 | near-intronic (+19 nt from the splice site) |
|---|---|---|
| SpliceAI | <0.2 | all four deltas below 0.2 · T>C here scores Δ0.95 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -1.6 |
| Non-coding constraint | Z -0.62 | 1 kb window · o/e 1.04 · regional · uncalibrated |
| Overall | ||
| CADD | 0.115 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
35.2%
East Asian · 15,733/44,684 alleles
Filtering AF
34.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 34.6%
Overall
7.47%
119,603/1,601,362 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 35.2% | 3 |
| Admixed American | 32.8% | 3 |
| South Asian | 22.1% | 5 |
| Middle Eastern | 8.59% | 12 |
| Remaining individualsnot grpmax-eligible | 7.97% | 13 |
| Finnishnot grpmax-eligible | 6.47% | 15 |
| African / African-American | 4.56% | 22 |
| European (non-Finnish) | 4.32% | 23 |
| Ashkenazi Jewishnot grpmax-eligible | 3.52% | 28 |
| Amishnot grpmax-eligible | 0.329% | 304 |
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
- ACAA2
- Coding
- c.753+19A>T
- MANE Select
- NM_006111
- Type
- single nucleotide variant
- Location
- chr18:49792133 (GRCh38)
- Gene constraint
- LOEUF 1.148 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.49 · 2 PDB
Similar variants
- ACAA2 p.Tyr198Asn Benign ★★ same type
- ACAA2 p.Ala183Thr Uncertain significance ★ ⚠ same type
- ACAA2 p.Ala196Thr Uncertain significance ★ ⚠ same type
- ACAA2 p.Ala250Thr Uncertain significance ★ ⚠ same type
- ACAA2 p.Ala267Gly Uncertain significance ★ ⚠ same type
- ACAA2 p.Ala70Ser Uncertain significance ★ ⚠ same type
- ACAA2 p.Arg133His Uncertain significance ★ ⚠ same type
- ACAA2 p.Arg371Cys 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/acaa2-c-753-plus-19a-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown