ACTB p.Ser348=
c.1044G>A · rs13447409 · VCV381956
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.633%, amr)
Conditions
2
developmental malformations-deafness-dystonia syndrome
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 -5.6 | GERP -3.7 |
| Overall | ||
| CADD | 9.085 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.633%
Admixed American · 379/59,836 alleles
Filtering AF
0.581%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.56%
Overall
0.0245%
395/1,612,224 alleles · rare
exomes 364/1,461,684 · genomes 31/150,540 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.633% | 158 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,921 |
| South Asian | 0.0033% | 30,322 |
| European (non-Finnish) | 0.000509% | 196,574 |
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
- ACTB
- Protein
- p.Ser348=
- Coding
- c.1044G>A
- MANE Select
- NM_001101
- dbSNP
- rs13447409
- Type
- single nucleotide variant
- Location
- chr7:5527832 (GRCh38)
- Gene constraint
- LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 95.31 · 93 PDB
Similar variants
- ACTB p.Ser348Leu Pathogenic/Likely pathogenic ★★ same residue
- ACTB p.Ala22Thr Likely pathogenic ★★ same condition
- ACTB p.Ala7Thr Likely pathogenic ★★ same condition
- ACTB p.Arg147Cys Pathogenic ★★ same condition
- ACTB p.Arg183Trp Pathogenic ★★ same condition
- ACTB p.Arg196Cys Pathogenic ★★ same condition
- ACTB p.Arg196His Pathogenic ★★ same condition
- ACTB p.Arg196Leu Likely pathogenic ★★ 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/actb-p-ser348 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown