AFAP1 p.Asn686=
c.2058C>T · rs185989039 · VCV2602924
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.064%, 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 -1.2 | GERP -3.6 |
| Overall | ||
| CADD | 5.578 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.064%
African / African-American · 48/75,008 alleles
Filtering AF
0.0495%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0444%
Overall
0.00545%
88/1,614,016 alleles · ultra-rare
exomes 58/1,461,716 · genomes 30/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.064% | 1,563 |
| Middle Eastern | 0.0165% | 6,056 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,627 |
| Admixed American | 0.00333% | 29,998 |
| European (non-Finnish) | 0.00271% | 36,874 |
| East Asian | 0.00223% | 44,884 |
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.Asn686=
- Coding
- c.2058C>T
- MANE Select
- NM_001134647
- dbSNP
- rs185989039
- Type
- single nucleotide variant
- Location
- chr4:7774743 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.09
Similar variants
- AFAP1 p.Val288Ala Uncertain significance ★★ ⚠ same type
- AFAP1 p.Ala783= 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
- AFAP1 p.Ala624Val Uncertain significance ★ ⚠ same type
- AFAP1 p.Ala682Thr 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-asn686 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown