MFN2 p.Phe56=
c.168C>T · rs769831339 · VCV2416460
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -0.41, phastCons 1 |
| Overall | ||
| CADD | 10.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,984 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000124%
2/1,613,978 alleles · very rare
exomes 2/1,461,772 · genomes 0/152,206 · 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.Phe56=
- Coding
- c.168C>T
- MANE Select
- NM_014874
- dbSNP
- rs769831339
- Type
- single nucleotide variant
- Location
- chr1:11989336 (GRCh38)
- Gene constraint
- LOEUF 0.602 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 81.94 · 3 PDB
- Residue 56
- the 'part of a helix bundle domain, formed by helices from n-terminal and c-terminal regions' region; an α-helix
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-phe56 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown