AFDN p.Ala1409=
c.4227G>A · rs62427711 · VCV2657134
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.494%, afr)
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 -15 | GERP -3.1 |
| Overall | ||
| CADD | 0.281 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.494%
African / African-American · 371/75,052 alleles
Filtering AF
0.453%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.437%
Overall
0.113%
1,825/1,614,038 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.494% | 202 |
| European (non-Finnish) | 0.117% | 852 |
| Remaining individualsnot grpmax-eligible | 0.0784% | 1,275 |
| Admixed American | 0.02% | 5,000 |
| Finnishnot grpmax-eligible | 0.00781% | 12,800 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| South Asian | 0.0022% | 45,521 |
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
- AFDN
- Protein
- p.Ala1409=
- Coding
- c.4227G>A
- MANE Select
- NM_001386888
- dbSNP
- rs62427711
- Type
- single nucleotide variant
- Location
- chr6:167951581 (GRCh38)
- Gene constraint
- LOEUF 0.398 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.69 · 6 PDB
- Residue 1409
- the 'disordered' region
Similar variants
- AFDN p.Ile438Val Uncertain significance ★★ ⚠ same type
- AFDN c.4968+1G>C Uncertain significance ★ same type
- AFDN p.Arg1634Leu Uncertain significance ★ ⚠ same type
- AFDN p.Arg1717Ter Uncertain significance ★ same type
- AFDN p.Arg999His Uncertain significance ★ ⚠ same type
- AFDN p.Asp1176Glu Uncertain significance ★ ⚠ same type
- AFDN p.Asp1516Ala Uncertain significance ★ ⚠ same type
- AFDN p.Asp539His 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/afdn-p-ala1409 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown