Is MFN2 p.Asp77= (c.231C>T) pathogenic?

MFN2 p.Asp77= (c.231C>T) is classified Likely benign in MFN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-03). Ultra-rare (popmax 0.0267%, eas); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with MFN2 p.Asp77= (c.231C>T)?

MFN2 p.Asp77= (c.231C>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is MFN2 p.Asp77= (c.231C>T) in the general population?

MFN2 p.Asp77= (c.231C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

MFN2 p.Asp77=

c.231C>T · rs763489927 · VCV705366

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -13	GERP -5.5
Overall
CADD	0.699	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,896 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00471% 76/1,614,016 alleles · ultra-rare exomes 71/1,461,886 · genomes 5/152,130 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,741
Remaining individualsnot grpmax-eligible	0.0128%	7,810
Admixed American	0.00833%	11,998
European (non-Finnish)	0.00407%	24,584
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,006

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.Asp77=
Coding: c.231C>T
MANE Select: NM_014874
dbSNP: rs763489927
Type: single nucleotide variant
Location: chr1:11992610 (GRCh38)
Gene constraint: LOEUF 0.602 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 3 PDB
Residue 77: the 'part of a helix bundle domain, formed by helices from n-terminal and c-terminal regions' region; an α-helix

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-asp77 (accessed [today's date]).

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