Is MFF p.Trp286Arg (c.856T>C) pathogenic?

MFF p.Trp286Arg (c.856T>C) is classified Uncertain significance in MFF (ClinVar, Single submitter, 2 submitters; last evaluated 2020-07-28). AlphaMissense: likely pathogenic (0.9941); Absent from gnomAD v4.1; Associated with encephalopathy due to defective mitochondrial and peroxisomal fission 2.

What condition is associated with MFF p.Trp286Arg (c.856T>C)?

MFF p.Trp286Arg (c.856T>C) is associated with encephalopathy due to defective mitochondrial and peroxisomal fission 2 (ClinVar).

How common is MFF p.Trp286Arg (c.856T>C) in the general population?

MFF p.Trp286Arg (c.856T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MFF p.Trp286Arg (c.856T>C)?

AlphaMissense predicts likely pathogenic (score 0.9941) — an in-silico prediction, not a clinical call.

MFF p.Trp286Arg

c.856T>C · rs2076297587 · VCV1030331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

encephalopathy due to defective mitochondrial and peroxisomal fission 2

Computational evidence

Protein change
AlphaMissense	0.9941	likely pathogenic · top 1% in MFF
REVEL	0.613	indeterminate
SaProt	LLR -15.33	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 26 kb · p 0.33 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM W337R vs ClinVar W286R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MFF
Protein: p.Trp286Arg
Coding: c.856T>C
MANE Select: NM_001277062
dbSNP: rs2076297587
Type: single nucleotide variant
Location: chr2:227357097 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 64.74

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

Disease context

encephalopathy due to defective mitochondrial and peroxisomal fission 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Encephalopathy due to mitochondrial and peroxisomal fission defect (Orphanet):

Onset: Childhood, Infancy, Neonatal

Similar variants

MFF p.Asp75Asn Uncertain significance ★★ ⚠ same condition
MFF p.Ile250Ser Uncertain significance ★★ ⚠ same condition
MFF p.Ala210= Benign/Likely benign ★★ same condition
MFF p.Pro31Leu Benign/Likely benign ★★ same condition
MFF c.-40-841T>G Likely pathogenic ★ same condition
MFF c.-40-842G>T Likely pathogenic ★ same condition
MFF p.Ile226Met Uncertain significance ★ ⚠ same condition
MFF p.Pro113Thr Uncertain significance ★ ⚠ 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/mff-p-trp286arg (accessed [today's date]).

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