FMN2 p.Ala995=
c.2985G>A · VCV4395856
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.01%, eas) — too common for a highly-penetrant pathogenic allele
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 -5 | GERP -1.6 |
| Overall | ||
| CADD | 6.577 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.01%
East Asian · 1,056/21,098 alleles
Filtering AF
4.75%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.65%
Overall
2.98%
18,321/614,636 alleles · common
exomes 17,772/587,426 · genomes 549/27,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 5.01% | 20 |
| African / African-American | 5.01% | 20 |
| Ashkenazi Jewishnot grpmax-eligible | 4.77% | 21 |
| Middle Eastern | 4.47% | 22 |
| Remaining individualsnot grpmax-eligible | 3.68% | 27 |
| Finnishnot grpmax-eligible | 2.99% | 33 |
| South Asian | 2.95% | 34 |
| European (non-Finnish) | 2.79% | 36 |
| Admixed American | 1.94% | 52 |
| Amishnot grpmax-eligible | 1.2% | 83 |
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.Ala995=
- Coding
- c.2985G>A
- MANE Select
- NM_020066
- Type
- single nucleotide variant
- Location
- chr1:240207797 (GRCh38)
- Gene constraint
- LOEUF 0.51 · pLI 0.51 (gnomAD)
- Structure
- AlphaFold pLDDT 51.48 · 2 PDB
- Residue 995
- the fh1 domain; the 'disordered' region
Similar variants
- FMN2 p.Ala995Val Likely benign ★ same residue
- 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
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-ala995 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown