ACTL9 p.Ser263Cys
c.788C>G · rs374419357 · VCV3141686
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.146%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.274 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.7 | GERP -2.1, phastCons 0.65 |
| Regional constraint | o/e 1.05 | unconstrained · MANE · 1,247 bp · p 0.2 · regional, not allelic |
| Overall | ||
| CADD | 18.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.146%
South Asian · 133/91,082 alleles
Filtering AF
0.126%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.118%
Overall
0.0154%
249/1,613,634 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.146% | 685 |
| Middle Eastern | 0.0825% | 1,212 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,473 |
| Admixed American | 0.0183% | 5,457 |
| European (non-Finnish) | 0.00653% | 15,325 |
| African / African-American | 0.004% | 25,008 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| East Asian | 0.00223% | 44,874 |
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.Ser263Cys
- Coding
- c.788C>G
- MANE Select
- NM_178525
- dbSNP
- rs374419357
- Type
- single nucleotide variant
- Location
- chr19:8697914 (GRCh38)
- Gene constraint
- LOEUF 1.575 · pLI 0.19 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56
Similar variants
- ACTL9 p.Ser263Phe Uncertain significance ★ same residue
- 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
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-ser263cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown