AFAP1 p.Pro513Leu
c.1538C>T · VCV3503195
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0342%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.024 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 2.9 | GERP -2.5, phastCons 0.99 |
| Regional constraint | o/e 1.14 | unconstrained · MANE · 108 kb · p 3.6e-06 · regional, not allelic |
| Overall | ||
| CADD | 17.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0342%
East Asian · 14/40,926 alleles
Filtering AF
0.0207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0165%
Overall
0.00303%
47/1,551,560 alleles · ultra-rare
exomes 44/1,399,432 · genomes 3/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0342% | 2,923 |
| Remaining individualsnot grpmax-eligible | 0.00998% | 10,019 |
| South Asian | 0.00714% | 14,007 |
| Finnishnot grpmax-eligible | 0.00334% | 29,951 |
| European (non-Finnish) | 0.00166% | 60,369 |
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.Pro513Leu
- Coding
- c.1538C>T
- MANE Select
- NM_001134647
- Type
- single nucleotide variant
- Location
- chr4:7781620 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.09
- Residue 513
- the 'disordered' region
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-pro513leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown