Is MFF p.Pro113Thr (c.337C>A) pathogenic?

MFF p.Pro113Thr (c.337C>A) is classified Uncertain significance in MFF (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.0999); Absent from gnomAD v4.1; Associated with encephalopathy due to defective mitochondrial and peroxisomal fission 2.

What condition is associated with MFF p.Pro113Thr (c.337C>A)?

MFF p.Pro113Thr (c.337C>A) is associated with encephalopathy due to defective mitochondrial and peroxisomal fission 2 (ClinVar).

How common is MFF p.Pro113Thr (c.337C>A) in the general population?

MFF p.Pro113Thr (c.337C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MFF p.Pro113Thr (c.337C>A)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

MFF p.Pro113Thr

c.337C>A · rs1414317381 · VCV634511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

encephalopathy due to defective mitochondrial and peroxisomal fission 2

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 26 kb · p 0.33 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 P139T vs ClinVar P113T) — 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.Pro113Thr
Coding: c.337C>A
MANE Select: NM_001277062
dbSNP: rs1414317381
Type: single nucleotide variant
Location: chr2:227332574 (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.Trp286Arg 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-pro113thr (accessed [today's date]).

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