Is MFF p.Thr95fs (c.284del) pathogenic?

MFF p.Thr95fs (c.284del) is classified Pathogenic in MFF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-27). Very rare (popmax 0.00267%, afr); Associated with encephalopathy due to defective mitochondrial and peroxisomal fission 2.

What condition is associated with MFF p.Thr95fs (c.284del)?

MFF p.Thr95fs (c.284del) is associated with encephalopathy due to defective mitochondrial and peroxisomal fission 2 (ClinVar).

How common is MFF p.Thr95fs (c.284del) in the general population?

MFF p.Thr95fs (c.284del) is very rare (popmax 0.00267%, afr) (gnomAD).

MFF p.Thr95fs

c.284del · rs1285225437 · VCV545568

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

encephalopathy due to defective mitochondrial and peroxisomal fission 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,916 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,518 alleles · very rare exomes 2/1,461,334 · genomes 1/152,184 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,458
European (non-Finnish)	8.48e-05%	1,179,587

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: MFF
Protein: p.Thr95fs
Coding: c.284del
MANE Select: NM_001277062
dbSNP: rs1285225437
Type: Deletion
Location: chr2:227332521 (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.Thr95Met Uncertain significance ★★ same residue
MFF p.Thr95= Benign ★★ same residue
MFF p.Glu127fs Pathogenic ★ same condition
MFF p.Pro54fs Likely pathogenic same condition
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

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-thr95fs (accessed [today's date]).

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