ACTN2 c.126+3C>T
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.92e-05%, nfe)
Conditions
2
dilated cardiomyopathy 1AA
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +3 | donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 19.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.92e-05%
European (non-Finnish) · 1/1,120,626 alleles
Overall
7.42e-05%
1/1,348,290 alleles · very rare
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.126+3C>T
- MANE Select
- NM_001103
- dbSNP
- rs1665886801
- Type
- single nucleotide variant
- Location
- chr1:236686802 (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-126-plus-3c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown