AFAP1 p.Glu705=
c.2115G>A · rs115587641 · VCV730676
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.68%, 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 -0.71 | GERP 0.67, phastCons 0.008 |
| Overall | ||
| CADD | 12.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.68%
African / African-American · 1,261/75,064 alleles
Filtering AF
1.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.57%
Overall
0.0881%
1,421/1,613,418 alleles · low-frequency
exomes 692/1,461,060 · genomes 729/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.68% | 60 |
| Admixed American | 0.118% | 845 |
| Remaining individualsnot grpmax-eligible | 0.109% | 919 |
| Middle Eastern | 0.0495% | 2,021 |
| South Asian | 0.0022% | 45,543 |
| European (non-Finnish) | 0.00136% | 73,751 |
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.Glu705=
- Coding
- c.2115G>A
- MANE Select
- NM_001134647
- dbSNP
- rs115587641
- Type
- single nucleotide variant
- Location
- chr4:7772958 (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.Asn686= Likely 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-glu705 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown