FLI1 p.Ser376=
c.1128G>A · rs766521149 · VCV2868563
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
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 -3.6 | GERP -4.2 |
| Overall | ||
| CADD | 1.437 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/60,014 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00675%
109/1,613,904 alleles · ultra-rare
exomes 105/1,461,708 · genomes 4/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 6,001 |
| European (non-Finnish) | 0.00831% | 12,040 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
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
- FLI1
- Protein
- p.Ser376=
- Coding
- c.1128G>A
- MANE Select
- NM_002017
- dbSNP
- rs766521149
- Type
- single nucleotide variant
- Location
- chr11:128810757 (GRCh38)
- Gene constraint
- LOEUF 0.367 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 64.32 · 14 PDB
Similar variants
- FLI1 p.Ala178Thr Uncertain significance ★★ ⚠ same type
- FLI1 p.Ala247Thr Uncertain significance ★★ ⚠ same type
- FLI1 p.Ala295Ser Uncertain significance ★★ ⚠ same type
- FLI1 p.Ala419Thr Uncertain significance ★★ ⚠ same type
- FLI1 p.Arg177His Uncertain significance ★★ ⚠ same type
- FLI1 p.Arg177Pro Uncertain significance ★★ ⚠ same type
- FLI1 p.Arg257Gln Uncertain significance ★★ ⚠ same type
- FLI1 p.Asn435Ser 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/fli1-p-ser376 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown