ACTL9 p.Arg35Gln
c.104G>A · rs376440765 · VCV2248737
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.144 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -2.2 |
| Regional constraint | o/e 1.05 | unconstrained · MANE · 1,247 bp · p 0.2 · regional, not allelic |
| Overall | ||
| CADD | 0.628 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
African / African-American · 15/75,022 alleles
Filtering AF
0.0123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00988%
Overall
0.00149%
24/1,612,136 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.02% | 5,001 |
| South Asian | 0.0022% | 45,465 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,400 |
| European (non-Finnish) | 0.000509% | 196,446 |
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
- ACTL9
- Protein
- p.Arg35Gln
- Coding
- c.104G>A
- MANE Select
- NM_178525
- dbSNP
- rs376440765
- Type
- single nucleotide variant
- Location
- chr19:8698598 (GRCh38)
- Gene constraint
- LOEUF 1.575 · pLI 0.19 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56
- Residue 35
- the 'disordered' region
Similar variants
- ACTL9 p.Ala174Asp Uncertain significance ★ same type
- ACTL9 p.Ala174Thr Uncertain significance ★ same type
- ACTL9 p.Ala187Ser Uncertain significance ★ same type
- ACTL9 p.Ala319Ser Uncertain significance ★ same type
- ACTL9 p.Ala361Thr Uncertain significance ★ same type
- ACTL9 p.Ala388Asp Uncertain significance ★ same type
- ACTL9 p.Ala392Gly Uncertain significance ★ same type
- ACTL9 p.Arg130Leu 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/actl9-p-arg35gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown