ACTL6B p.Asn233=
c.699C>T · rs140422470 · VCV2571288
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.597%, mid)
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 4 | GERP 2.9, phastCons 1 |
| Overall | ||
| CADD | 9.288 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.597%
Middle Eastern · 36/6,032 alleles
Filtering AF
0.443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.39%
Overall
0.0854%
1,374/1,609,146 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.597% | 168 |
| Admixed American | 0.122% | 816 |
| European (non-Finnish) | 0.0962% | 1,039 |
| African / African-American | 0.0787% | 1,271 |
| Remaining individualsnot grpmax-eligible | 0.0754% | 1,326 |
| South Asian | 0.0255% | 3,915 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0103% | 9,737 |
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
- ACTL6B
- Protein
- p.Asn233=
- Coding
- c.699C>T
- MANE Select
- NM_016188
- dbSNP
- rs140422470
- Type
- single nucleotide variant
- Location
- chr7:100647504 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.52
- Residue 233
- a UniProt-annotated variant site (in dee76)
Similar variants
- ACTL6B p.Asn233fs Likely pathogenic ★ same residue
- ACTL6B p.Arg97Ter Likely pathogenic ★★ same type
- ACTL6B p.Gln186Ter Pathogenic/Likely pathogenic ★★ same type
- ACTL6B p.Gln278Ter Likely pathogenic ★★ same type
- ACTL6B p.Gly343Arg Pathogenic/Likely pathogenic ★★ same type
- ACTL6B p.Gly349Ser Likely pathogenic ★★ same type
- ACTL6B p.Trp247Ter Likely pathogenic ★★ same type
- ACTL6B p.Arg363Gln 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/actl6b-p-asn233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown