Is MFN2 p.Ser593= (c.1779G>A) pathogenic?

MFN2 p.Ser593= (c.1779G>A) is classified Likely benign in MFN2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-05-27). Rare (popmax 0.243%, eas); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with MFN2 p.Ser593= (c.1779G>A)?

MFN2 p.Ser593= (c.1779G>A) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is MFN2 p.Ser593= (c.1779G>A) in the general population?

MFN2 p.Ser593= (c.1779G>A) is rare (popmax 0.243%, eas) (gnomAD).

MFN2 p.Ser593=

c.1779G>A · rs367623682 · VCV476767

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.243%, 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 -1.5	GERP -3.7
Overall
CADD	4.843	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.243% East Asian · 109/44,884 alleles

Filtering AF 0.206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.192%

Overall 0.0106% 171/1,614,178 alleles · rare exomes 159/1,461,888 · genomes 12/152,290 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.243%	412
Ashkenazi Jewishnot grpmax-eligible	0.098%	1,021
South Asian	0.0187%	5,358
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	0.00102%	98,337

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.Ser593=
Coding: c.1779G>A
MANE Select: NM_014874
dbSNP: rs367623682
Type: single nucleotide variant
Location: chr1:12006600 (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 p.Ser593Thr Uncertain significance ★★ ⚠ same residue
MFN2 p.Ser593Leu 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

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-ser593 (accessed [today's date]).

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