AFAP1 p.Asn580Asp
c.1738A>G · rs533448738 · VCV2519335
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0928%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.076 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 1.14 | unconstrained · MANE · 108 kb · p 3.6e-06 · regional, not allelic |
| Overall | ||
| CADD | 18.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0928%
East Asian · 38/40,928 alleles
Filtering AF
0.0695%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0614%
Overall
0.00296%
46/1,551,966 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0928% | 1,077 |
| South Asian | 0.00714% | 14,009 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,192 |
| European (non-Finnish) | 8.72e-05% | 1,147,072 |
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
- AFAP1
- Protein
- p.Asn580Asp
- Coding
- c.1738A>G
- MANE Select
- NM_001134647
- dbSNP
- rs533448738
- Type
- single nucleotide variant
- Location
- chr4:7781420 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.09
Similar variants
- AFAP1 p.Asn580Ser Uncertain significance ★ same residue
- AFAP1 p.Val288Ala Uncertain significance ★★ ⚠ same type
- AFAP1 p.Ala783= Likely benign ★★ same type
- AFAP1 p.Asn686= Likely benign ★★ same type
- AFAP1 p.Glu705= Benign ★★ same type
- AFAP1 p.Ala438Ser Uncertain significance ★ ⚠ same type
- AFAP1 p.Ala534Ser Uncertain significance ★ same type
- AFAP1 p.Ala587Val 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/afap1-p-asn580asp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown