ACTA2 c.129+57A>C
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.53%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +57 | deep intronic (+57 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.8 | GERP -3.2 |
| Non-coding constraint | Z 2.78 | 1 kb window · o/e 0.80 · regional · uncalibrated |
| Overall | ||
| CADD | 0.018 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.53%
African / African-American · 2,644/74,892 alleles
Filtering AF
3.42%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.37%
Overall
0.19%
3,055/1,610,034 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.53% | 28 |
| Remaining individualsnot grpmax-eligible | 0.286% | 350 |
| Middle Eastern | 0.234% | 428 |
| Admixed American | 0.212% | 472 |
| South Asian | 0.00879% | 11,373 |
| European (non-Finnish) | 0.00714% | 14,009 |
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
- ACTA2
- Coding
- c.129+57A>C
- MANE Select
- NM_001613
- dbSNP
- rs115232613
- Type
- single nucleotide variant
- Location
- chr10:88948745 (GRCh38)
- Gene constraint
- LOEUF 0.472 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 95.43
Similar variants
- ACTA2 p.Arg118Gln Pathogenic/Likely pathogenic ★★ same type
- ACTA2 p.Arg149Cys Pathogenic ★★ same type
- ACTA2 p.Arg149Leu Pathogenic/Likely pathogenic ★★ same type
- ACTA2 p.Arg179Cys Pathogenic ★★ same type
- ACTA2 p.Arg179His Pathogenic ★★ same type
- ACTA2 p.Arg198Cys Pathogenic/Likely pathogenic ★★ same type
- ACTA2 p.Arg198His Pathogenic/Likely pathogenic ★★ same type
- ACTA2 p.Arg256Cys 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/acta2-c-129-plus-57a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown