Is MFN2 p.Ser609= (c.1827C>T) pathogenic?

MFN2 p.Ser609= (c.1827C>T) is classified Benign/Likely benign in MFN2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-14). Rare (popmax 0.28%, mid); Associated with Charcot-Marie-Tooth disease.

What condition is associated with MFN2 p.Ser609= (c.1827C>T)?

MFN2 p.Ser609= (c.1827C>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is MFN2 p.Ser609= (c.1827C>T) in the general population?

MFN2 p.Ser609= (c.1827C>T) is rare (popmax 0.28%, mid) (gnomAD).

MFN2 p.Ser609=

c.1827C>T · rs138724074 · VCV214636

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.28%, mid)

Conditions

Charcot-Marie-Tooth disease

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 -2.1	GERP -4
Overall
CADD	7.824	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.28% Middle Eastern · 17/6,062 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.0513% 828/1,614,134 alleles · rare exomes 757/1,461,880 · genomes 71/152,254 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.378%	264
Middle Easterngrpmax	0.28%	357
Remaining individualsnot grpmax-eligible	0.0944%	1,060
South Asian	0.0527%	1,898
European (non-Finnish)	0.0489%	2,045
Admixed American	0.015%	6,669
African / African-American	0.008%	12,503

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser609=
Coding: c.1827C>T
MANE Select: NM_014874
dbSNP: rs138724074
Type: single nucleotide variant
Location: chr1:12006648 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 2

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.Arg104Gln 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-ser609 (accessed [today's date]).

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