AFDN p.Ile297=
c.891C>T · rs369829441 · VCV2657133
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.132%, mid)
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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -7.4 | GERP -3.6 |
| Overall | ||
| CADD | 1.896 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.132%
Middle Eastern · 8/6,058 alleles
Filtering AF
0.0657%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.048%
Overall
0.00824%
133/1,613,354 alleles · rare
exomes 117/1,461,084 · genomes 16/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.132% | 757 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,840 |
| Admixed American | 0.0217% | 4,613 |
| European (non-Finnish) | 0.00712% | 14,043 |
| East Asian | 0.00669% | 14,937 |
| African / African-American | 0.00267% | 37,505 |
| South Asian | 0.0011% | 90,938 |
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.Ile297=
- Coding
- c.891C>T
- MANE Select
- NM_001386888
- dbSNP
- rs369829441
- Type
- single nucleotide variant
- Location
- chr6:167880511 (GRCh38)
- Gene constraint
- LOEUF 0.398 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.69 · 6 PDB
- Residue 297
- the ras-associating 2 domain
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-ile297 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown