Is MFN2 p.Pro576= (c.1728C>T) pathogenic?

MFN2 p.Pro576= (c.1728C>T) is classified Benign/Likely benign in MFN2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Rare (popmax 0.121%, afr); Associated with Inborn genetic diseases.

What condition is associated with MFN2 p.Pro576= (c.1728C>T)?

MFN2 p.Pro576= (c.1728C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is MFN2 p.Pro576= (c.1728C>T) in the general population?

MFN2 p.Pro576= (c.1728C>T) is rare (popmax 0.121%, afr) (gnomAD).

MFN2 p.Pro576=

c.1728C>T · rs147802404 · VCV516493

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.121%, afr)

Conditions

Inborn genetic diseases

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 -8.9	GERP -3.7
Overall
CADD	0.211	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.121% African / African-American · 91/75,050 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0936%

Overall 0.00595% 96/1,614,220 alleles · rare exomes 45/1,461,872 · genomes 51/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.121%	825
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00167%	60,030
European (non-Finnish)	8.47e-05%	1,180,043

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.Pro576=
Coding: c.1728C>T
MANE Select: NM_014874
dbSNP: rs147802404
Type: single nucleotide variant
Location: chr1:12006549 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 2

Similar variants

MFN2 p.Pro576Leu Uncertain significance ★ ⚠ same residue
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

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-pro576 (accessed [today's date]).

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