ACTN2 p.Glu77Ter
c.229G>T · rs1572112489 · VCV829879
Likely pathogenic
No assertion criteria
Classification
Likely pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
dilated cardiomyopathy 1AA
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 21 |
| Splicing | ||
| SpliceAI | Δ0.99 | donor gain · deltas |
| Pangolin | Δ0.65 | gain · loss 0.27 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.3, phastCons 1 |
| Overall | ||
| CADD | 58.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ACTN2
- Protein
- p.Glu77Ter
- Coding
- c.229G>T
- MANE Select
- NM_001103
- dbSNP
- rs1572112489
- Type
- single nucleotide variant
- Location
- chr1:236717960 (GRCh38)
- Gene constraint
- LOEUF 0.432 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.88 · 18 PDB
- Residue 77
- the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region
Similar variants
- ACTN2 p.Glu77= Likely benign ★ same residue
- 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
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-p-glu77ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown