ACTN1 p.Pro188=
c.564C>T · VCV3710424
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0143%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.1 | |
| Overall | ||
| CADD | 6.214 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0143%
South Asian · 13/91,080 alleles
Filtering AF
0.00844%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00661%
Overall
0.00719%
116/1,614,068 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0143% | 7,006 |
| European (non-Finnish) | 0.00805% | 12,421 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,625 |
| Finnishnot grpmax-eligible | 0.00313% | 31,990 |
| East Asian | 0.00223% | 44,886 |
| African / African-American | 0.00133% | 75,042 |
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.Pro188=
- Coding
- c.564C>T
- MANE Select
- NM_001130004
- Type
- single nucleotide variant
- Location
- chr14:68909348 (GRCh38)
- Gene constraint
- LOEUF 0.331 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.39 · 4 PDB
- Residue 188
- the calponin-homology (ch) 2 domain; an α-helix; the 'actin-binding' region
Similar variants
- 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
- ACTN1 p.Ala48Val 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-pro188 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown