ARMC9 p.Pro447=
c.1341G>A · rs59475942 · VCV780872
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 8.19%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.06 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.3 | GERP -3.1 |
| Overall | ||
| CADD | 1.439 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.19%
African / African-American · 6,143/75,006 alleles
Filtering AF
8.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.95%
Overall
0.426%
6,882/1,614,042 alleles · common
exomes 3,435/1,461,804 · genomes 3,447/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.19% | 12 |
| Remaining individualsnot grpmax-eligible | 0.55% | 182 |
| Admixed American | 0.438% | 228 |
| Middle Eastern | 0.264% | 379 |
| South Asian | 0.0274% | 3,643 |
| European (non-Finnish) | 0.00754% | 13,258 |
| East Asian | 0.00446% | 22,438 |
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
- ARMC9
- Protein
- p.Pro447=
- Coding
- c.1341G>A
- MANE Select
- NM_001352754
- dbSNP
- rs59475942
- Type
- single nucleotide variant
- Location
- chr2:231276642 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.71
Similar variants
- ARMC9 p.Pro447Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- ARMC9 c.1773+1G>A Likely pathogenic ★★ same type
- ARMC9 c.178-1G>A Likely pathogenic ★★ same type
- ARMC9 c.178-2A>C Likely pathogenic ★★ same type
- ARMC9 p.Arg299Ter Pathogenic/Likely pathogenic ★★ same type
- ARMC9 p.Arg343Cys Pathogenic/Likely pathogenic ★★ same type
- ARMC9 p.Arg87Ter Pathogenic/Likely pathogenic ★★ same type
- ARMC9 p.Thr293= Pathogenic/Likely pathogenic ★★ 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/armc9-p-pro447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown