ACTN1 p.Ala884Val
c.2651C>T · rs199901015 · VCV1326697
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1405 | likely benign |
|---|---|---|
| REVEL | 0.383 | indeterminate |
| SaProt | LLR -10.85 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | phastCons 1 |
| Regional constraint | o/e 1.30 | unconstrained · MANE · 2,221 bp · p 0.0072 · regional, not allelic |
| Overall | ||
| CADD | 25.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A862V vs ClinVar A884V) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0581% | 1,722 |
| Middle Easterngrpmax | 0.0164% | 6,082 |
| European (non-Finnish) | 0.00864% | 11,568 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| South Asian | 0.0011% | 91,086 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- ACTN1
- Protein
- p.Ala884Val
- Coding
- c.2651C>T
- MANE Select
- NM_001130004
- dbSNP
- rs199901015
- Type
- single nucleotide variant
- Location
- chr14:68874953 (GRCh38)
- Gene constraint
- LOEUF 0.331 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.39 · 4 PDB
- Residue 884
- a turn
Similar variants
- ACTN1 p.Ala884= Likely benign ★ same residue
- ACTN1 p.Arg450Cys Pathogenic/Likely pathogenic ★★ same type
- ACTN1 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same type
- ACTN1 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same type
- ACTN1 p.Glu225Lys Pathogenic ★★ same type
- ACTN1 p.Leu547Pro Likely pathogenic ★★ ⚠ same type
- ACTN1 p.Val105Ile Pathogenic/Likely pathogenic ★★ same type
- ACTN1 p.Ala255Val Uncertain significance ★★ ⚠ 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/actn1-p-ala884val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown