AFAP1 p.His215=
c.645C>T · rs62640877 · VCV708393
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.872%, 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 -4.1 |
| Overall | ||
| CADD | 5.135 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.872%
African / African-American · 654/75,020 alleles
Filtering AF
0.816%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.794%
Overall
0.0456%
736/1,614,114 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.872% | 115 |
| Remaining individualsnot grpmax-eligible | 0.0656% | 1,524 |
| Admixed American | 0.0583% | 1,715 |
| South Asian | 0.0022% | 45,537 |
| European (non-Finnish) | 0.000339% | 295,010 |
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.His215=
- Coding
- c.645C>T
- MANE Select
- NM_001134647
- dbSNP
- rs62640877
- Type
- single nucleotide variant
- Location
- chr4:7838605 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.09
- Residue 215
- the ph 1 domain
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.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
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-his215 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown