FLAD1 p.Pro506=
c.1518A>G · rs369428195 · VCV2084528
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0762%, 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 | GERP -3.8 |
| Overall | ||
| CADD | 1.778 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0762%
African / African-American · 57/74,820 alleles
Filtering AF
0.0603%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0546%
Overall
0.00378%
61/1,611,970 alleles · ultra-rare
exomes 33/1,459,792 · genomes 28/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0762% | 1,313 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,789 |
| European (non-Finnish) | 8.48e-05% | 1,179,038 |
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
- FLAD1
- Protein
- p.Pro506=
- Coding
- c.1518A>G
- MANE Select
- NM_025207
- dbSNP
- rs369428195
- Type
- single nucleotide variant
- Location
- chr1:154990492 (GRCh38)
- Gene constraint
- LOEUF 0.809 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.34 · 2 PDB
- Residue 506
- the 'fad synthase' region; a β-strand
Similar variants
- FLAD1 p.Arg148Ter Pathogenic ★★ same type
- FLAD1 p.Arg249Ter Pathogenic ★★ same type
- FLAD1 p.Arg530Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- FLAD1 p.Cys136Ter Pathogenic/Likely pathogenic ★★ same type
- FLAD1 c.1365-3A>G Uncertain significance ★★ same type
- FLAD1 p.Arg137Gln Uncertain significance ★★ ⚠ same type
- FLAD1 p.Arg137Trp Uncertain significance ★★ ⚠ same type
- FLAD1 p.Arg169His 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/flad1-p-pro506 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown