MFN2 p.Phe452=
c.1356C>T · rs1639320282 · VCV2093634
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 6.2e-05%)
Conditions
1
Charcot-Marie-Tooth disease type 2
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 1 | GERP -0.002, phastCons 1 |
| Overall | ||
| CADD | 12.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.2e-05%
Overall
6.2e-05%
1/1,614,054 alleles · very rare
exomes 0/1,461,872 · genomes 1/152,182 · joint denominator
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
- MFN2
- Protein
- p.Phe452=
- Coding
- c.1356C>T
- MANE Select
- NM_014874
- dbSNP
- rs1639320282
- Type
- single nucleotide variant
- Location
- chr1:12004577 (GRCh38)
- Gene constraint
- LOEUF 0.602 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 81.94 · 3 PDB
Similar variants
- MFN2 c.1160+1G>A Likely pathogenic ★★ same condition
- MFN2 c.475-1G>C Pathogenic ★★ same condition
- MFN2 p.Ala166Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MFN2 p.Ala220Thr Pathogenic/Likely pathogenic ★★ same condition
- MFN2 p.Ala383Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MFN2 p.Ala738Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MFN2 p.Arg104Trp Pathogenic ★★ same condition
- MFN2 p.Arg259Cys Pathogenic/Likely pathogenic ★★ same condition
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/mfn2-p-phe452 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown