FDFT1 p.Pro249=
c.747G>A · rs146586993 · VCV3049597
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.998%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.93 | GERP -3.8 |
| Overall | ||
| CADD | 5.133 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.998%
South Asian · 909/91,072 alleles
Filtering AF
0.944%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.923%
Overall
0.128%
2,062/1,613,946 alleles · rare
exomes 1,935/1,461,678 · genomes 127/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.998% | 100 |
| Remaining individualsnot grpmax-eligible | 0.149% | 672 |
| Finnishnot grpmax-eligible | 0.116% | 865 |
| European (non-Finnish) | 0.0799% | 1,251 |
| Admixed American | 0.0517% | 1,936 |
| Middle Eastern | 0.0165% | 6,062 |
| African / African-American | 0.0107% | 9,378 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,867 |
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
- FDFT1
- Protein
- p.Pro249=
- Coding
- c.747G>A
- MANE Select
- NM_004462
- dbSNP
- rs146586993
- Type
- single nucleotide variant
- Location
- chr8:11830288 (GRCh38)
- Gene constraint
- LOEUF 1.764 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.14 · 32 PDB
- Residue 249
- an α-helix
Similar variants
- FDFT1 p.Pro249Arg Uncertain significance ★ ⚠ same residue
- FDFT1 p.Pro249Leu Uncertain significance ★ ⚠ same residue
- FDFT1 c.100-85G>C Uncertain significance ★★ same type
- FDFT1 p.Ala333Ser Uncertain significance ★★ ⚠ same type
- FDFT1 p.Asn265Ser Uncertain significance ★★ ⚠ same type
- FDFT1 p.Gly151Asp Uncertain significance ★★ ⚠ same type
- FDFT1 p.Ile252Thr Uncertain significance ★★ ⚠ same type
- FDFT1 p.Phe210Leu 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/fdft1-p-pro249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown