FLAD1 p.Ser247=
c.741C>T · VCV4701590
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9 | GERP -3.5 |
| Overall | ||
| CADD | 1.819 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
African / African-American · 13/75,068 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00155%
25/1,614,246 alleles · ultra-rare
exomes 18/1,461,890 · genomes 7/152,356 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0173% | 5,774 |
| East Asian | 0.0111% | 8,977 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
| South Asian | 0.0011% | 91,088 |
| European (non-Finnish) | 0.000339% | 295,011 |
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.Ser247=
- Coding
- c.741C>T
- MANE Select
- NM_025207
- Type
- single nucleotide variant
- Location
- chr1:154988473 (GRCh38)
- Gene constraint
- LOEUF 0.809 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.34 · 2 PDB
- Residue 247
- the 'fad diphosphatase' 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-ser247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown