Is MFN2 p.Pro590= (c.1770A>G) pathogenic?

MFN2 p.Pro590= (c.1770A>G) is classified Likely benign in MFN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). Ultra-rare (popmax 0.0178%, eas); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with MFN2 p.Pro590= (c.1770A>G)?

MFN2 p.Pro590= (c.1770A>G) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is MFN2 p.Pro590= (c.1770A>G) in the general population?

MFN2 p.Pro590= (c.1770A>G) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

MFN2 p.Pro590=

c.1770A>G · rs776537176 · VCV1107861

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

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 -7.2	GERP -3.7
Overall
CADD	0.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,898 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000558% 9/1,614,076 alleles · ultra-rare exomes 7/1,461,890 · genomes 2/152,186 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,612
South Asian	0.0011%	91,094

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.Pro590=
Coding: c.1770A>G
MANE Select: NM_014874
dbSNP: rs776537176
Type: single nucleotide variant
Location: chr1:12006591 (GRCh38)
Gene constraint: LOEUF 0.602 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 3 PDB

Full MFN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro590 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown