ACTN2 c.2154+19C>T
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
dilated cardiomyopathy 1AA
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +19 | near-intronic (+19 nt from the splice site) |
|---|---|---|
| SpliceAI | Δ0.81 | donor gain · deltas |
| Pangolin | Δ0.76 | gain · loss 0.11 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.44 | GERP -1.2 |
| Overall | ||
| CADD | 24.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,026 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000547%
8/1,461,620 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,026 |
| African / African-American | 0.00133% | 75,058 |
| South Asian | 0.0011% | 91,084 |
| European (non-Finnish) | 0.000424% | 236,004 |
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
- ACTN2
- Coding
- c.2154+19C>T
- MANE Select
- NM_001103
- dbSNP
- rs1484623448
- Type
- single nucleotide variant
- Location
- chr1:236755217 (GRCh38)
- Gene constraint
- LOEUF 0.432 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.88 · 18 PDB
Similar variants
- ACTN2 p.Ala119Thr Pathogenic/Likely pathogenic ★★ same condition
- ACTN2 p.Thr247Met Likely pathogenic ★★ same condition
- ACTN2 c.1107+3G>A Uncertain significance ★★ same condition
- ACTN2 c.1108-10A>G Uncertain significance ★★ same condition
- ACTN2 c.1255+1G>C Uncertain significance ★★ same condition
- ACTN2 c.126+2T>G Uncertain significance ★★ same condition
- ACTN2 c.127-3C>A Uncertain significance ★★ same condition
- ACTN2 c.1974+4A>G Uncertain significance ★★ same condition
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/actn2-c-2154-plus-19c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown