AFAP1L2 p.Arg730=
c.2190C>T · rs115650575 · VCV773541
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.433%, 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 -4.4 | GERP -3.5 |
| Overall | ||
| CADD | 0.181 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.433%
African / African-American · 325/75,052 alleles
Filtering AF
0.394%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.379%
Overall
0.0289%
467/1,613,864 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.433% | 231 |
| Remaining individualsnot grpmax-eligible | 0.0496% | 2,016 |
| Middle Eastern | 0.033% | 3,031 |
| Finnishnot grpmax-eligible | 0.0251% | 3,983 |
| Admixed American | 0.0183% | 5,457 |
| South Asian | 0.011% | 9,107 |
| East Asian | 0.00669% | 14,957 |
| European (non-Finnish) | 0.00585% | 17,102 |
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
- AFAP1L2
- Protein
- p.Arg730=
- Coding
- c.2190C>T
- MANE Select
- NM_001001936
- dbSNP
- rs115650575
- Type
- single nucleotide variant
- Location
- chr10:114297337 (GRCh38)
- Gene constraint
- LOEUF 0.605 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.56 · 1 PDB
Similar variants
- AFAP1L2 p.Arg730Cys Uncertain significance ★ ⚠ same residue
- AFAP1L2 p.Arg648His Uncertain significance ★★ ⚠ same type
- VWA2 p.Arg682Trp Benign ★★ ⚠ same type
- VWA2 p.Asn331= Benign ★★ same type
- VWA2 p.Gly641= Likely benign ★★ same type
- VWA2 p.His496Tyr Benign ★★ same type
- VWA2 p.Phe365= Benign ★★ same type
- VWA2 p.Pro544= Benign ★★ 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/afap1l2-p-arg730 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown