FMN2 p.Thr133=
c.399C>T · rs375101837 · VCV1336408
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0661%, nfe)
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 -2.1 | GERP -3 |
| Overall | ||
| CADD | 7.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0661%
European (non-Finnish) · 778/1,177,354 alleles
Filtering AF
0.0622%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0606%
Overall
0.0524%
843/1,607,722 alleles · ultra-rare
exomes 778/1,455,732 · genomes 65/151,990 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0661% | 1,513 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0612% | 1,634 |
| Remaining individualsnot grpmax-eligible | 0.0418% | 2,392 |
| Finnishnot grpmax-eligible | 0.0143% | 7,006 |
| African / African-American | 0.00936% | 10,681 |
| Admixed American | 0.00678% | 14,741 |
| South Asian | 0.00111% | 90,408 |
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
- FMN2
- Protein
- p.Thr133=
- Coding
- c.399C>T
- MANE Select
- NM_020066
- dbSNP
- rs375101837
- Type
- single nucleotide variant
- Location
- chr1:240092508 (GRCh38)
- Gene constraint
- LOEUF 0.51 · pLI 0.51 (gnomAD)
- Structure
- AlphaFold pLDDT 51.48 · 2 PDB
- Residue 133
- the 'disordered' region
Similar variants
- FMN2 p.Ile183Phe Likely pathogenic ★★ ⚠ same type
- FMN2 p.Ala1691Val Uncertain significance ★★ ⚠ same type
- FMN2 p.Ala367Val Uncertain significance ★★ ⚠ same type
- FMN2 p.Ala508Val Uncertain significance ★★ ⚠ same type
- FMN2 p.Asp352Tyr Uncertain significance ★★ ⚠ same type
- FMN2 p.Gln192Leu Uncertain significance ★★ ⚠ same type
- FMN2 p.Gln210Arg Uncertain significance ★★ ⚠ same type
- FMN2 p.Gly244Ala 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/fmn2-p-thr133 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown