ACTL6B p.Arg76Gln
c.227G>A · VCV3365584
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3785 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3785 | ambiguous |
|---|---|---|
| REVEL | 0.905 | moderately pathogenic-leaning |
| SaProt | LLR -8.40 | tolerated |
| ⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 4.9, phastCons 1 |
| Regional constraint | o/e 0.69 | unconstrained · MANE · 9,273 bp · p 1.9e-09 · regional, not allelic |
| Overall | ||
| CADD | 34.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ACTL6B
- Protein
- p.Arg76Gln
- Coding
- c.227G>A
- MANE Select
- NM_016188
- Type
- single nucleotide variant
- Location
- chr7:100655462 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.52
- Residue 76
- the 'essential for mediating its function in dendritic development; may contribute to neuronal-specific targeting' region
Similar variants
- 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
- ACTL6B p.Glu297Lys 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-arg76gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown