ACTB p.Tyr218=
c.654C>T · rs781745429 · VCV1639760
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00878%, sas)
Conditions
1
Baraitser-Winter syndrome 1
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 -8.5 | GERP -3.7 |
| Overall | ||
| CADD | 1.001 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00878%
South Asian · 8/91,092 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.00105%
17/1,614,016 alleles · very rare
exomes 14/1,461,762 · genomes 3/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00878% | 11,386 |
| African / African-American | 0.00801% | 12,491 |
| European (non-Finnish) | 0.000254% | 393,349 |
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.Tyr218=
- Coding
- c.654C>T
- MANE Select
- NM_001101
- dbSNP
- rs781745429
- Type
- single nucleotide variant
- Location
- chr7:5528429 (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.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
- ACTB p.Arg206Gln Pathogenic/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-tyr218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown