AFAP1 p.Gly516Ser
c.1546G>A · rs368001545 · VCV2654641
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0665%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.033 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.38 | GERP -1.7, phastCons 0.033 |
| Regional constraint | o/e 1.14 | unconstrained · MANE · 108 kb · p 3.6e-06 · regional, not allelic |
| Overall | ||
| CADD | 13.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0665%
Middle Eastern · 4/6,014 alleles
Filtering AF
0.0227%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0185%
Overall
0.00535%
83/1,551,636 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0665% | 1,503 |
| South Asian | 0.0309% | 3,233 |
| Admixed American | 0.00588% | 16,995 |
| Remaining individualsnot grpmax-eligible | 0.00499% | 20,036 |
| European (non-Finnish) | 0.00401% | 24,935 |
| East Asian | 0.00244% | 40,932 |
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.Gly516Ser
- Coding
- c.1546G>A
- MANE Select
- NM_001134647
- dbSNP
- rs368001545
- Type
- single nucleotide variant
- Location
- chr4:7781612 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.09
- Residue 516
- 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-gly516ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown