FMNL1 p.Phe640=
c.1920C>T · rs946321398 · VCV2647846
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
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 4.1 | GERP 0.86, phastCons 1 |
| Overall | ||
| CADD | 12.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,080 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.000743%
12/1,614,000 alleles · ultra-rare
exomes 8/1,461,760 · genomes 4/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,040 |
| African / African-American | 0.00534% | 18,734 |
| Admixed American | 0.00333% | 30,000 |
| East Asian | 0.00223% | 44,906 |
| European (non-Finnish) | 0.000254% | 393,317 |
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
- FMNL1
- Protein
- p.Phe640=
- Coding
- c.1920C>T
- MANE Select
- NM_005892
- dbSNP
- rs946321398
- Type
- single nucleotide variant
- Location
- chr17:45242375 (GRCh38)
- Gene constraint
- LOEUF 0.483 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 75.17 · 1 PDB
- Residue 640
- the fh2 domain
Similar variants
- FMNL1 c.895-3C>T Benign ★★ same type
- FMNL1 c.1885+2T>A Uncertain significance ★ same type
- FMNL1 p.Ala1012Thr Uncertain significance ★ ⚠ same type
- FMNL1 p.Ala157Gly Uncertain significance ★ same type
- FMNL1 p.Ala16Val Uncertain significance ★ ⚠ same type
- FMNL1 p.Ala31Glu Uncertain significance ★ ⚠ same type
- FMNL1 p.Ala386Val Uncertain significance ★ ⚠ same type
- FMNL1 p.Ala409Val 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/fmnl1-p-phe640 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown