ACTN4 p.Phe153=
c.459C>T · rs201314541 · VCV799878
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.9 | GERP -4.9 |
| Overall | ||
| CADD | 11.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,080 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00116%
Overall
0.00192%
31/1,614,218 alleles · very rare
exomes 29/1,461,882 · genomes 2/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,770 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,256 |
| European (non-Finnish) | 0.00203% | 49,168 |
| African / African-American | 0.00133% | 75,062 |
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
- ACTN4
- Protein
- p.Phe153=
- Coding
- c.459C>T
- MANE Select
- NM_004924
- dbSNP
- rs201314541
- Type
- single nucleotide variant
- Location
- chr19:38704995 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.66 · 5 PDB
- Residue 153
- the calponin-homology (ch) 1 domain; a UniProt-annotated variant site (in fsgs1; uncertain significance); an α-helix; the 'actin-binding' region
Similar variants
- ACTN4 p.Phe153Leu Uncertain significance ★ ⚠ same residue
- ACTN4 p.Phe153Ser Likely pathogenic same residue
- ACTN4 p.Lys255Glu Pathogenic ★★ same type
- ACTN4 c.1443-7C>T Uncertain significance ★★ same type
- ACTN4 c.2190+5G>A Uncertain significance ★★ same type
- ACTN4 c.2190+6C>T Uncertain significance ★★ same type
- ACTN4 p.Ala475Thr Uncertain significance ★★ ⚠ same type
- ACTN4 p.Ala759Thr 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/actn4-p-phe153 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown