ACTN1 p.Pro295=
c.885G>A · rs139710798 · VCV2046272
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.903%, 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 -15 | |
| Overall | ||
| CADD | 0.836 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.903%
South Asian · 822/91,062 alleles
Filtering AF
0.851%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.831%
Overall
0.0877%
1,415/1,613,596 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.903% | 111 |
| Middle Eastern | 0.264% | 379 |
| Ashkenazi Jewishnot grpmax-eligible | 0.24% | 417 |
| Remaining individualsnot grpmax-eligible | 0.0928% | 1,078 |
| European (non-Finnish) | 0.0363% | 2,756 |
| Admixed American | 0.0133% | 7,502 |
| African / African-American | 0.012% | 8,336 |
| East Asian | 0.00446% | 22,442 |
| Finnishnot grpmax-eligible | 0.00157% | 63,830 |
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.Pro295=
- Coding
- c.885G>A
- MANE Select
- NM_001130004
- dbSNP
- rs139710798
- Type
- single nucleotide variant
- Location
- chr14:68892254 (GRCh38)
- Gene constraint
- LOEUF 0.331 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.39 · 4 PDB
- Residue 295
- the 'interaction with ddn' region
Similar variants
- ACTN1 p.Pro295Leu Uncertain significance ★★ ⚠ 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-pro295 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown