Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 61.9%, afr) — 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 +331 | deep intronic (+331 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.6 | GERP -0.39 |
| Non-coding constraint | Z 0.64 | 1 kb window · o/e 0.95 · regional · uncalibrated |
| Overall | ||
| CADD | 4.189 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
61.9%
African / African-American · 25,595/41,362 alleles
Filtering AF
61.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 61%
Overall
39.7%
60,322/151,876 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 61.9% | 2 |
| East Asian | 56.2% | 2 |
| Admixed American | 41.4% | 2 |
| Remaining individualsnot grpmax-eligible | 39.8% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 38.7% | 3 |
| Middle Eastern | 33.2% | 3 |
| European (non-Finnish) | 28.3% | 4 |
| South Asian | 27.2% | 4 |
| Finnishnot grpmax-eligible | 23.8% | 4 |
| Amishnot grpmax-eligible | 20.8% | 5 |
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
- ACAD9
- Coding
- c.346+331C>A
- MANE Select
- NM_014049
- dbSNP
- rs1680781
- Type
- single nucleotide variant
- Location
- chr3:128893987 (GRCh38)
- Gene constraint
- LOEUF 0.884 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.09 · 2 PDB
Similar variants
- ACAD9 c.1030-1G>A Pathogenic/Likely pathogenic ★★ same type
- ACAD9 c.1150-2A>G Likely pathogenic ★★ same type
- ACAD9 c.1278+1G>T Likely pathogenic ★★ same type
- ACAD9 c.1279-2A>C Likely pathogenic ★★ same type
- ACAD9 c.1358+2T>G Likely pathogenic ★★ same type
- ACAD9 c.1359-1G>A Pathogenic/Likely pathogenic ★★ same type
- ACAD9 c.1563+1G>A Pathogenic/Likely pathogenic ★★ same type
- ACAD9 c.1A>G Pathogenic/Likely pathogenic ★★ 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/acad9-c-346-plus-331c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown